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B Gustafsson

Publications and source records attributed to B Gustafsson.

At least 37 records · Page 2Linked to original sources
PubMed2001

Vesicle release probability and pre-primed pool at glutamatergic synapses in area CA1 of the rat neonatal hippocampus.

Factors determining the release probability were examined using whole-cell patch-clamp recording and minimal stimulation (10 impulses, 50 Hz) of individual glutamatergic synapses, containing single release sites, on pyramidal neurones in the CA1 region of hippocampal slices from neonatal rats. Release probability following the first action potential in the burst (P1) varied among the synapses from 0 to 0.87 (mean +/- s.d.; 0.35 +/- 0.28, n = 52) and the average release during the burst (burst pool) varied from 0.4 to 4.1 events (1.7 +/- 0.85, n = 52). Heterogeneity in P1 did not co-vary with that of the burst pool. By selecting burst trials during which only one release event occurred, the vesicle release probability (Pves) at a release site could be determined. It was found to vary considerably among the synapses, from 0.04 to 0.94 (0.43 +/- 0.28, n = 43). This heterogeneity correlated significantly with that of P1 such that more than half of the variation of P1 could be explained by a variation in Pves. The average number of vesicles directly available for release at the onset of the burst (the pre-primed pool) was estimated as the cumulative release up to that point in the burst where a second release event did not produce higher initial release probability than that found in trials where only one vesicle was released. The average pre-primed pool varied among the synapses from 0.4 to 2.1 (1.03 +/- 0.42, n = 43). It co-varied significantly with that of P1 such that it could explain the remaining variation in P1. The difference between the burst pool and the pre-primed pool suggests the presence of a fast (< 100 ms), activity-dependent priming of vesicles. Some synapses (9/52) did not show any initial release (P1 = 0), but release occurred later during the burst ('low frequency mute synapses'). Their behaviour was explained by an absence of a pre-primed pool.

Action Potentials↗
PubMed2001

An ethnic role for chronic, but not acute, graft-versus-host disease after HLA-identical sibling stem cell transplantation.

Among 424 HLA identical siblings undergoing stem cell transplantation, 364 were Scandinavians and 60 represented other ethnic groups. The cumulative probabilities of acute graft-versus-host disease grades II-IV were similar in both groups, 17% in Scandinavians and 12% in the others, p = 0.4. In a multivariate analysis, less effective immune suppression with cyclosporine or methotrexate alone (p = 0.001), recipient seropositive for three to four herpes viruses (p = 0.004), CMV-seropositive recipient (p = 0.05) and early engraftment (before day 15) (p = 0.05) were independent risk-factors for acute GVHD grades II-IV. The cumulative probabilities of chronic GVHD were 47% and 68% in the two ethnic populations, respectively (p = 0.004). In multivariate analysis, higher patient age (p < 0.001), non-Scandinavian population (p < 0.001) and immunised female donor to male recipient (p = 0.03) were independent risk factors for chronic GVHD. The higher incidence of chronic GVHD could not be explained by differences in HLA antigen frequencies. The cumulative probabilities of relapse were 37% in the both groups. This suggests that the Scandinavian population is more homogeneous with regard to minor histocompatibility antigens important for chronic, but not acute GVHD.

Acute Disease↗
PubMed2001

Gut mucosal uptake and retention characteristics contribute to the high intestinal selectivity of budesonide compared with prednisolone in the rat.

BACKGROUND: Budesonide and prednisolone are both effective for the treatment of inflammatory bowel disease, but budesonide produces fewer adverse systemic effects. High first-pass hepatic inactivation of budesonide partially explains its favourable ratio between topical and systemic activity, but it is probable that its uptake and retention in intestinal target tissues are also contributory. AIM: To compare the uptake and retention of radio-labelled budesonide and prednisolone in rat ileal mucosa in vivo. METHODS: 3H-Budesonide and 3H-prednisolone were applied for 10 min directly to a perfused segment of rat ileum in vivo, followed by saline lavage every 10 min. Steroid uptake into the mucosa and submucosa was assessed at 20 min and 4 h. The uptake of budesonide was also measured in allergen-challenged animals vs. saline-challenged controls to assess whether inflammation of the mucosa with ongoing plasma exudation would impair its uptake. RESULTS: Budesonide was better absorbed into ileal tissue (15-fold at 20 min) than prednisolone and better retained (50-fold at 4 h) after topical administration. The uptake of budesonide was not impaired by exudation processes following allergen challenge. CONCLUSIONS: The higher uptake and retention characteristics of budesonide in gut mucosa should contribute to its greater intestinal selectivity compared with that of prednisolone.

Administration, Topical↗
PubMed2001

Topical and oral anti-inflammatory activity of budesonide compared with oral prednisolone in an animal model using allergen-induced gut mucosal exudation of plasma as a marker.

BACKGROUND: Development of topically active glucocorticosteroids with minimal systemic effects is paramount in improving therapy in inflammatory bowel disease. Our experimental model in the rat has proved useful for assessing topical versus systemic anti-inflammatory potency of glucocorticosteroids on the inflamed gut. METHODS: Experiments were performed on allergen-sensitized perfused rat ileum in vivo. Mucosal exudation of plasma, induced by local allergen perfusion, was measured as the appearance of circulating 125I-labelled albumin in the gut lumen. Experiments compared the anti-exudative effects of oral budesonide (0.1 mg/kg) with oral prednisolone (1, 3.3 or 10 mg/kg) and saline, given by oral gavage 24 h prior to allergen challenge, and of topical budesonide (3 x 10(-5) mol/L) with saline, administered in the perfusate 4 h prior to allergen challenge. Systemic glucocorticosteroid activity was assessed by weighing thymus glands after sacrifice. RESULTS: Allergen-induced plasma exudation was significantly reduced by oral budesonide, oral prednisolone (dose-dependently) and topically applied budesonide; topical budesonide was effective within 4 h. While prednisolone significantly reduced the relative thymus weight at both 3.3 and 10 mg/kg, budesonide given orally, 0.1 mg/kg, or topically, 3 x 10(-5) mol/L, had no significant effect. CONCLUSION: Budesonide, administered orally or topically, shows higher selectivity for the gut mucosa than prednisolone and produces local anti-inflammatory responses comparable to prednisolone, without the accompanying systemic effects.

Administration, Oral↗
PubMed2001

MDM2 and p53 in childhood acute lymphoblastic leukemia: higher expression in childhood leukemias with poor prognosis compared to long-term survivors.

In previous studies the authors have found increased expression of p53 and MDM2 proteins in leukemic cells in a majority of children eligible for bone marrow transplantation (BMT) due to relapse or prognostically unfavorable features. In this study the immunohistochemical expression of p53, MDM2, and p21Cip1 was investigated in bone marrow samples from the time of diagnosis in 30 children with acute lymphoblastic leukemia (ALL) surviving disease-free at least 5 years. This group was compared with 15 advanced ALL patients, admitted for BMT. In 7 of the BMT patients orginal diagnostic marrow samples were also available for analysis. Four out of 30 ALL patients in the relapse-free group expressed p53 in the original leukemic cell population, while 8/15 advanced ALL patients did before BMT (p = .014). Four out of 30 cases in the relapse-free group expressed MDM2, while 10/15 in the BMT group did (p = .0011). In retrospect, MDM2 overexpression at the time of diagnosis was also more common (p = .0098) in the BMT group as well as p53 overexpression (p = .054) compared to nonrelapsed patients.

Adolescent↗
PubMed2000

[A questionnaire study in the county of Stockholm on transmission control of chlamydia infections. Too many physicians neglect the contact tracing].

Since 1989 the reporting of chlamydia infections is regulated by the Contagious Diseases Act, which stipulates that a physician who detects chlamydia is obliged to trace the patient's sexual partner(s). Up to 1994 the annual decrease in the number of chlamydia cases was 20 percent, which did not meet the goal stipulated by the County Council. A questionnaire study was carried out concerning diagnosis, treatment and public health intervention in chlamydia patients seen by general and private practitioners. While the clinical management was seen to adhere to the recommendations of the National Board of Health, adequate tracing of sexual contacts was not carried out in 20-45 per cent of the cases. In a major urban area, such as the County of Stockholm, referral of all chlamydia cases to specialist clinics could possibly improve not only the care of the patients but also the success rate in reaching their sex partners.

Adolescent↗
PubMed2000

Cellular expression of MDM2 and p53 in childhood leukemias with poor prognosis.

BACKGROUND: Previous studies have suggested that altered expression or dysfunction of the tumor suppressor gene p53 or the oncogene MDM2 could indicate disease progression in children with leukemia who would fail to achieve complete remission or who would relapse. While these studies mainly have described aberrations of MDM2 and p53 function at the DNA and mRNA-level, we have examined p53 and MDM2 expression at the protein level. Mutation of the p53 tumor suppressor gene may result in cellular accumulation of the p53 protein, due to prolonged half-life of the abnormal protein. The p53 protein can also be rendered nonfunctional by overexpression of proteins that bind to p53, such as MDM2. Both pathways have been proposed to disrupt cell cycle regulation in humans. Recent studies have shown that increased expressions of MDM2 as well as of p53 can be detected at the protein level in the absence of gene amplification. PROCEDURE: Forty-three bone marrow samples were analyzed immunohistochemically for p53 and MDM2. Twenty-nine bone marrow samples were obtained in children with active, prognostically unfavorable leukemia and MDS. Fourteen bone marrow samples were from children with non-malignant hematological disorders. RESULTS: p53 protein was expressed in 12 patients and MDM2 in 17 patients with leukemia. In the control group MDM2 expression was detected in one child, while p53 was not found in any of the samples. CONCLUSIONS: Our findings of p53 or MDM2 positive cells in a majority of children with unfavorable prognostic features suggests that dysfunction of the p53-dependent cell growth control have a role in the development of high risk leukemias.

Adolescent↗
PubMed2000

The liver protective effect of ischemic preconditioning may be mediated by adenosine.

We investigated the involvement of adenosine in ischemic preconditioning (IPC) by the unspecific antagonist, 8-phenyltheophylline (8-PT). Anesthetized Wistar rats were treated as follows: 1. non-ischemic controls, 2. ischemic controls: 60 min of clamping of the common hepatic artery followed by 60 min reperfusion, 3. IPC: 10 min ischemia followed by 15 min reperfusion, prior to the identical ischemia-reperfusion (IR) period as in group 2, 4. 8-PT + IPC: 8-PT 10 mg/kg i.v. was given 10 min prior to the identical procedure as in group 3. The peripheral liver blood flow was monitored by laser-Doppler flowmetry. Blood alanine aminotransferase (ALT) was analyzed once every 60 min. IPC significantly reduced impairment of liver blood flow, as well as ALT increase during reperfusion. This effect was abolished by pretreatment with 8-PT. Adenosine appears to be a crucial effector in IPC. Clinical studies need to be undertaken to explore a possible effect of IPC in liver transplantation.

Adenosine↗
PubMed2000

Space-time clustering of childhood lymphatic leukaemias and non-Hodgkin's lymphomas in Sweden.

BACKGROUND: The discussion concerning clusters of childhood leukaemia has mainly been focused on their relation to the time and place of diagnosis. Recently some studies have indicated clustering not only at diagnosis, but also around time and place of birth. Space-time clustering at time of birth could be of special interest if the aetiological agent is of infectious origin and the induction of leukaemia either occurs pre- or perinatally or an infection at that time favours a poor subsequent immune response to the agent. METHODS: To identify possible space-time clustering we have used the close-pair method of Knox. One-thousand-twenty recorded cases (0-14 years) of childhood acute lymphatic leukaemia and 293 cases (0-14 years) of malignant non-Hodgkin's lymphoma from Sweden between 1973-1996 were analysed. The records include date of birth and of diagnosis as well as addresses at birth and at diagnosis. RESULTS: A significant excess of case-pairs (25 observed, 14.9 expected, p = 0.01) was observed close in date and place of birth in the 4-14 year age group with acute lymphatic leukaemia (ALL). However there was no statistically significant clustering found around time of diagnosis. When the cases of leukaemia and the non-Hodgkin's lymphomas were combined no statistically significant clustering was obtained neither at birth nor at diagnosis. CONCLUSIONS: This study strengthens the evidence of space-time clustering around the birth date in children whom later developed ALL. This observation is in support of the hypothesis that pre- or perinatal infections can induce a process leading to ALL.

Adolescent↗
PubMed2000

Popliteal pterygium syndrome in a Swedish family--clinical findings and genetic analysis with the van der Woude syndrome locus at 1q32-q41.

The present study describes a Swedish family in which the mother and her son were affected with signs of popliteal pterygium syndrome (PPS, OMIM 119500). Both individuals had bilateral complete cleft lip and palate, oral synechiae, paramedian pits on the lower lip, toe syndactyly and a piece of triangular skin overgrowth on the great toes. The son also presented with soft tissue syndactyly of the 2nd and 3rd fingers. Although popliteal pterygium was not found, the above clinical features were diagnostic for PPS. Chromosomal abnormalities were not revealed in either case by cytogenetic analyses. A test for microdeletion in the VWS region at 1q32-q41 was performed in the family using 5 polymorphic microsatellite markers from the region. The affected son was found to be heterozygous for all 5 markers, suggesting that microdeletion at the VWS region was unlikely. The VWS locus, however, was not excluded by haplotype analysis of the family.

Abnormalities, Multiple↗
PubMed2000

On the direct Fourier method for computer tomography.

The paper considers the direct Fourier methods (DFM's) for reconstructing an image from its given X-ray projections. The main purpose here is to use concepts from numerical analysis to estimate the errors in the methods. We also suggest an alternative to the interpolations involved in the DFM's and estimate the number of terms involved. Realizing that one of the main reasons for the degradation of the quality of the reconstruction is the Gibbs phenomenon, we suggest a way to overcome this difficulty and give numerical evidence of its efficacy.

Algorithms↗
PubMed2000

Inhibitory effect of diabetes on proliferation of vascular smooth muscle after balloon injury in rat aorta.

UNLABELLED: The effect of streptozotocin-induced diabetes on cell proliferation in rat aortic intima-media, as well as on local gene expression of transforming growth factor-beta1 (TGF-beta1) was studied. TGF-beta1 mRNA was measured by solution hybridization and TGF-beta1 protein by ELISA. Proliferation was measured by bromodeoxyuridine incorporation into DNA two days after balloon injury. All BrdU-labelled cells observed were smooth muscle cells. After a diabetes duration of 2 and 4 weeks, labelled cells were significantly fewer compared with controls. Circulating levels of total TGF-beta1 were lowered in rats with 2 weeks diabetes. Although the balloon injury procedure by itself stimulated the gene expression of TGF-beta1, no significant difference in TGF-beta1 mRNA content between diabetic and control rats after injury was found. IN CONCLUSION: vascular smooth muscle proliferation in vivo is inhibited by the diabetic state in this model of insulin deficient diabetes and this inhibition is not related to an impaired local expression of TGF-beta1.

Angioplasty, Balloon↗
PubMed1999

On down-regulation of the immune response to metastatic malignant melanoma.

Treatment of metastatic malignant melanoma with interferon alpha (IFNalpha) results in objective remission in approximately 15% of patients. In a previous investigation, we found that about 50% of the patients achieved at least minor or short-lived remissions. In some tumours extensive areas of regressive tumour change occurred. However, even in these areas remnants of tumour cells were generally found. The short duration of the immune response in some patients and the incomplete eradication of the tumour can be due either to selection of non-immunogenic tumour cells or to down-regulation of the immune reactivity to the tumour. In the present paper, the expression of the zeta chain of the T cell receptor in CD3+ lymphocytes and the expression of CD28 in CD3+, CD4+ and CD8+ lymphocytes was studied in resectable melanoma metastases from 20 treated (IFNalpha or IFNalpha in combination with cisplatinum and dacarbazine) and 16 untreated patients. A double-staining technique was used, and the occurrence and distribution of lymphocytes showing down-regulation of the zeta chain or CD28 were separately registered in different areas of the metastases: close to the tumour cells in areas of unaffected tumour growth, in areas with regressive tumour changes, in areas with marked fibrosis and in stromal areas with densely packed lymphocytes. CD3+ zeta lymphocytes were found in all metastases, but their number and distribution varied considerably. Down-regulation of the zeta chain was most often found in areas of regressive changes. In contrast, T lymphocytes infiltrating close to the tumour cells had a stronger expression of the zeta chain (P = 0.016). Down-regulation was also found in stromal areas of densely packed lymphocytes and in areas of fibrosis. The pattern of down-regulation of CD28 in various subsets of lymphocytes was similar to that of zeta chain. The same pattern of down-regulation of CD28 and the zeta chain was found in both untreated and treated patients, indicating that the down-regulation is not due to treatment but to the release of immunosuppressor factors from areas with high tumour cell density or extensive destruction of tumour cells. These results concur well with the view that IFNalpha treatment can result in immune-mediated tumour cell destruction early in the treatment period and that this immune response to the tumour can be followed by immunosuppression within a few weeks.

Adult↗
PubMed1999

Evidence of space-time clustering of childhood acute lymphoblastic leukaemia in Sweden.

We have examined 645 recorded cases of childhood acute lymphatic leukaemia (ALL) in Sweden during 1973-89 to identify space-time clustering by using the close-pair method of Knox. The records included date of birth and of diagnosis as well as addresses at birth and at diagnosis. There was a significant excess of case pairs close in date of birth and place of birth in the 5- to 15-year age group.

Adolescent↗
PubMed1999

Expression of ICAM-1 during IFN-alpha-based treatment of metastatic malignant melanoma: relation to tumor-infiltrating mononuclear cells and regressive tumor changes.

Intercellular adhesion molecule-1 (ICAM-1) plays an important role in cell to cell interactions. In malignant melanoma, ICAM-1 expression correlates with malignant behavior. We used monoclonal antibodies, anti-ICAM-1, anti-CD4+, anti-CD8+, and anti-CD11c+ to study the effect of interferon-alpha (IFN-alpha) on the expression of ICAM-1 by melanoma cells in regional metastases and its correlation to the occurrence of CD4+, CD8+, and CD11c+ cells close to tumor cells and in the tumor stroma. We also estimated the expression of ICAM-1 and regressive changes in malignant melanoma metastases, correlating the duration of treatment to these effects of IFN-alpha. Twenty-three IFN-alpha-treated and 10 untreated patients with regional metastatic malignant melanoma were studied. The duration of IFN-alpha treatment influenced the expression of ICAM-1. In metastases from patients treated for 1 week only, 1 of 5 showed high expression of ICAM-1 compared with 6 of 11 of those treated for 3 weeks (p = 0.01, chi-square test for trend comparing untreated patients and patients with various durations of IFN-alpha treatment). In IFN-alpha-treated patients with low expression of ICAM-1, none of 7 metastases showed CD4+ cells infiltrating close to tumor cells, in contrast to 6 of 10 metastases expressing high amounts of ICAM-1 (p = 0.03). Similarly, the expression of ICAM-1 was found to correlate with the occurrence of CD8+ cells close to the tumor cells (p = 0.04). We also showed a correlation between ICAM-1 expression and histologic evidence of tumor regression (p = 0.02).

Adult↗
PubMed1999

Isolation and Spontaneous Resolution of Eight-Coordinate Stereoisomers.

The right- and left-handed propeller-shaped enantiomers of the eight-coordinate SmI(2) complexes shown can be resolved by crystallization from dimethoxyethane (dme) at ambient temperature. Apart from representing a new type of chiral metal complex, such enantiomers are potential reagents for enantioselective reductions.

Journal Article↗