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Biomedical subjects

M Bengtsson

Publications and source records attributed to M Bengtsson.

At least 37 records · Page 2Linked to original sources
PubMed2000

A more favourable clinical course of lymphoma relapsing after high-dose therapy: evidence of tumour heterogeneity?

Patients with Hodgkin's disease (HD) or large cell lymphomas who relapse after conventional chemotherapy have a poor prognosis without high-dose chemotherapy and stem cell transplantation (HDCT). Patients who relapse after HDCT have an extremely poor outcome. In the present study we describe four patients with relapsed HD (n=1) and large cell lymphomas (n=3) after HDCT. All had an aggressive clinical course before HDT. At relapse, however, they all have had prolonged remissions and/or spontaneous regressions on mild or no treatment. Possible explanations could be selection of less malignant clones or a lymphoma controlled by the immune system. The mechanisms are, however, unknown but warrant further studies of the molecular biology in these and similar cases.

Adult↗
PubMed2000

Antennal response of codling moth males, Cydia pomonella L. (Lepidoptera: Tortricidae), to the geometric isomers of codlemone and codlemone acetate.

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.

Animal Structures↗
PubMed1999

Nucleosome structural features and intrinsic properties of the TATAAACGCC repeat sequence.

Nucleosomes, the fundamental building blocks of chromatin, play an architectural role in ensuring the integrity of the genome and act as a regulator of transcription. Intrinsic properties of the underlying DNA sequence, such as flexibility and intrinsic bending, direct the formation of nucleosomes. We have earlier identified genomic nucleosome-positioning sequences with increased in vitro ability for nucleosome formation. One group of sequences bearing a 10-base pair consensus repeat sequence of TATAAACGCC had the highest reported nucleosome affinity from genomic material. Here, we report the intrinsic physical properties of this sequence and the structural details of the nucleosome it forms, as analyzed by footprinting techniques. The minor groove is buried toward the histone octamer at the AA steps and facing outwards at the CC steps. By cyclization kinetics, the overall helical repeat of the free DNA sequence was found to be 10.5 base pairs/turn. Our experiments also showed that this sequence is highly flexible, having a J-factor 25-fold higher than that of random sequence DNA. In addition, the data suggest that twist flexibility is an important determinant for translational nucleosome positioning, particularly over the dyad region.

Animals↗
PubMed1999

[Umbilical cord blood from unrelated donor. An alternative to bone marrow transplantation].

Unrelated umbilical cord blood (UCB) as a source of haematopoietic stem/progenitor cells has been used for the first time in Sweden for allografting two boys (6 and 11 1/2 years old) with acute leukaemia in complete remission. Double class-II HLA-mismatch UCB units, from the Milan and New York cord blood banks, respectively, were used. Pre-transplant preparation consisted in fractionated total body irradiation in both cases, followed by cytoreductive high-dose cyclophosphamide for the 6-year-old with acute lymphocytic leukaemia (ALL) and fludarabine-melphalan for the 11 1/2-year-old with acute non-lymphocytic leukaemia (ANLL). Despite delayed haematopoietic recovery (probably due to HLA disparity) or reactivated cytomegalovirus infection in one boy, the immediate post-graft course was uneventful and extramedullary toxicity mild in both cases. Only transient acute graft-versus-host disease occurred, and complete donor chimerism was confirmed. Unfortunately, the out-come was unfavourable in both cases, the ANLL patient succumbing on day 96 due to pneumonia followed by multiorgan failure, and the ALL patient on day 140 due to combined medullar and central nervous system relapse. Although UCB transplantation needs further evaluation, it may contribute substantially to successful salvage procedures. Thus the introduction of cord blood banking in Sweden merits consideration.

Blood Banks↗
PubMed1999

Linear reduction of clonal cells in stem cell enriched grafts in transplanted multiple myeloma.

In 30 patients with multiple myeloma who were scheduled for peripheral blood stem-cell transplantation, a quantitative analysis of the stem cells following enrichment by anti-CD34 was carried out. To detect the cells of the specific myeloma clone, polymerase chain reaction (PCR) was performed using unique allele-specific oligo primers for the immunoglobulin heavy chain rearrangement. The clonogenic cells before and after stem-cell enrichment, were quantified by a limiting dilution assay and a highly sensitive semi-nested PCR combined with a real-time quantitative PCR. In order to accomplish a statistically adequate end-point analysis, a large number of PCR analyses (40 per sample) were performed. By this technique the lowest detection limit observed was one myeloma cell per 106 cells. Myeloma cells were detected in 29/30 samples from the CD34-enriched fraction. The CD34 selection procedure resulted in a median 28-fold enrichment of CD34+ haemopoietic precursor cells. The stem-cell selection reduced the median concentration of clonal cells per million total cells by half, with a highly significant linear relationship between the number of myeloma cells before and after stem cell enrichment. The median depletion of clonal cells by the overall procedure was 2.15 log units, corresponding to a reduction of the total quantity of clonal cells reinfused into the patients by at least 99.3%. We conclude that CD34+ cell enrichment led to a reliable tumour cell depletion of the order of 2 log, which may not be sufficient since the total number of tumour cells in the leukapheresis product was 7.2 log (median).

Adolescent↗
PubMed1999

FEC mobilized stem cells for high-dose therapy in breast cancer patients. SB6 9401 Study Group.

The feasibility of mobilizing peripheral blood stem cells (PBSC) using anthracycline containing polychemotherapy and G-CSF on the first 50 patients randomized to the high-dose arm in the adjuvant SBG 9401 is investigated. The patients were treated with standard FEC (5-fluorouracil 600 mg/m2, epirubicin 60 mg/m2, cyclophosphamide 600 mg/m2) for two courses followed by a modified third FEC course with a C dose of 1200 mg/m2 supported with subcutaneous G-CSF (filgrastim) at 5 mg/kg followed by harvest around day 11. The mean yield of CD34+ cells per patient was 10.6x10(6)/kg (range 2.6-29.1). The side effects after the third course were low and only one patient developed an uncomplicated granulopenic fever. Our data indicated a correlation between number of transfused CD34+ cells and days to neutrophil and platelet recovery. In conclusion, the modified FEC regimen followed by G-CSF is a feasible method for PBSC mobilization in the adjuvant setting.

Antigens, CD34↗
PubMed1999

Analysis of mutations in exon 1 of the human thyrotropin receptor gene: high frequency of the D36H and P52T polymorphic variants.

The aim of the present study was to investigate the N-terminal part (the translated part of exon 1) of the human thyrotropin receptor (TSHR) for the presence of mutations. Patients with Graves' disease (n = 160) and healthy controls (blood donors; n = 140) were screened using single-stranded conformational polymorphism (SSCP) in combination with restriction enzyme digestion for the two previously known mutations in this part of the receptor, viz. D36H and P52T TSHR-variants. We did not find any novel mutation in this region. However, D36H and P52T variants were found both in the TSHR of Graves' patients and in the healthy controls. The overall frequency of the D36H-receptor variant was 5.0% (15/300) and of the P52T-receptor, 7.3% (22/300). There was no major difference in the frequency for either of the TSHR alleles between the 2 groups. Thus, these 2 polymorphic variants of the TSHR seem to occur in a relatively high frequency in the population.

Alleles↗
PubMed1999

Natural effector cells in patients with acute myeloid leukemia treated with the immunomodulator Linomide after autologous bone marrow transplantation.

Roquinimex, Linomide, is a quinoline derivative with pleiotropic immunomodulatory activities which has been shown to enhance NK function. As part of a phase III placebo-controlled multicenter study patients were randomized to receive Roquinimex, 0.2 mg/kg body weight, or a placebo twice weekly for a duration of 2 yr following autologous bone marrow transplantation for acute myeloid leukemia in remission. At Arhus University Hospital 7 patients were randomized to receive the active drug and 6 to receive the placebo. Surviving patients were followed for 2 yr with immunological monitoring of their natural immune effector cells (NK- and LAK cell activity). Peripheral heparinized blood samples were obtained twice before the onset of conditioning therapy and at several time points after ABMT, and whole blood samples were analyzed by flow cytometry for the detection of leukocyte differentiation antigens as well as by 4 h 51Cr release assays for cytotoxicity. In contrast to previous experience with Linomide, in the present study we found that at 36 wk or later time points Linomide patients exhibited a significant suppression of circulating natural effector cell number and activity when compared with the control group. These observations underline the need for further exploration into novel and manageable immunostimulators.

Acute Disease↗
PubMed1998

Convergent synthesis of neoglycopeptides by coupling of 2-bromoethyl glycosides to cysteine and homocysteine residues in T cell stimulating peptides.

The 2-bromoethyl beta-glycosides of the disaccharide galabiose [Gal(alpha1-4)Gal] and the trisaccharides globotriose [Gal(alpha1-4)Gal(beta1-4)Glc] and 3'-sialyllactose [Neu5Ac(alpha2-3)Gal(beta1-4)Glc] have been prepared by improved routes. The 2-bromoethyl glycosides were then used in cesium carbonate promoted alkylations of the sulfhydryl groups of cysteine and homocysteine residues in T cell stimulating peptides. This convergent and general approach was used to prepare 16 neoglycopeptides which were obtained in 52-95% yields after purification by HPLC. 1H NMR spectroscopy revealed that beta-elimination and epimerization of neoglycopeptide stereocentres did not occur during the synthesis.

Amino Acid Sequence↗
PubMed1998

Bone mineral density in patients with Crohn's disease during long-term treatment with azathioprine.

OBJECTIVES: To ascertain whether patients with Crohn's disease treated with azathioprine maintained bone mineral mass better than patients treated with steroids alone. DESIGN: Retrospective study. SETTING: University Hospital of Malmö, Sweden. SUBJECTS: A total of 59 patients with ileocolonic, ileocaecal or colonic Crohn's disease. METHODS: Bone mass was assessed by dual photon X-ray absorptiometry at the level of L2-L4. RESULTS: Patients treated with a high lifetime dose of steroids (> 5 g prednisolone) had significantly (P = 0.011) lower Z-score of L2-L4 (-0.87 +/- 1.11; 11 SD) than steroid-treated patients, who had received a low dose of prednisolone (< 5 g) (0.08 +/- 1.16 SD). Azathioprine did not negatively influence the steroid effect on bone mineral density. CONCLUSIONS: Azathioprine does not seem to affect bone mineral density by itself. However, by being steroid-saving, it seems to conserve bone mineral mass in patients with Crohn's disease.

Absorptiometry, Photon↗
PubMed1998

Effects of intravenous regional administration of methylprednisolone plus mepivacaine in rheumatoid arthritis.

To evaluate the subjective and objective response to intravenous regional administration of a glucocorticoid (IVRAG) on rheumatoid arthritis (RA), twenty RA-patients received, in a randomised, double-blind crossover and placebo-controlled fashion, either 50 mg methylprednisolone in mepivacaine 0.25% or mepivacaine (placebo) in one hand only using a Bier-block technique. The other hand was given the opposite. One week later the procedure was repeated but the previous placebo hand was now treated with the glucocorticoid. About 50% of the patients experienced a subjective improvement at 1 and 6 weeks. After one week a significant reduction was recorded in grip diastasis with no difference between the glucocorticoid and the placebo. In the other outcome measures (grip strength, handvolume, rest pain, and movement provoked pain) no differences were recorded between the glucocorticoid and placebo. At six weeks a significant reduction in grip diastasis and movement provoked pain as well as a significant increase in grip strength were noted. Hand volume was unchanged. IVRAG is a safe, easy and well-tolerated technique. The beneficial results are probably due to both a systemic and a regional effect. The findings of benefit in both hands at the end of one week seem to suggest that mepivacaine can give some short term improvement.

Adult↗
PubMed1998

Antibodies against double-stranded DNA and development of polymyositis during treatment with interferon.

Alpha interferons have become effective palliative treatments for patients with neuroendocrine tumours such as carcinoids and endocrine pancreatic tumours. However, several reports indicate an increased incidence of both autoantibodies and autoimmune diseases in patients treated with interferon-alpha (IFN-alpha). We studied the development of antibodies against double-stranded DNA (dsDNA) and clinical signs of autoimmune disease in 214 patients with malignant carcinoids or endocrine pancreatic tumours consecutively admitted for treatment with IFN-alpha. Seventeen patients (8%) developed antibodies against dsDNA, predominantly females (12 females and 5 males). One patient had clinical and laboratory signs of polymyositis. Among the other 16 patients, three developed hypothyroidism and in six patients the anti-dsDNA autoantibodies normalized despite continuing therapy. Although a significant number of patients developed autoantibodies against dsDNA, overt autoimmune disease related to these antibodies is a rare event and many patients spontaneously normalize these titres despite continuing IFN-alpha treatment.

Aged↗
PubMed1998

Hyperexcitability in fibromyalgia.

OBJECTIVE: Spontaneous chronic widespread pain in combination with hyperalgesia to pressure stimuli is the hallmark of fibromyalgia (FM). We tested whether muscular hyperalgesia can exist in a muscle without spontaneous pain, which could indicate a generalized hyperexcitability of the nociceptive system in patients with FM. METHODS: Twelve women with FM and 12 age matched female controls participated in this blind study. Patients had no spontaneous pain in the anterior tibial (AT) muscle. The pressure pain threshold was tested on the AT muscle. The pain threshold to electrical single and repeated stimulations of the skin and of the right AT muscle was assessed. Pain was evoked in the left AT muscle by infusion of sterile hypertonic saline (5.7%, 2.8 ml over 480 s). The saline induced muscle pain intensity and duration were assessed by continuous recordings on an electronic visual analog scale (VAS), and the distribution of pain was assessed on drawings. The sequence of electrical sensibility tests and the infusion of hypertonic saline was randomized. RESULTS: Pressure pain thresholds were lower (p < 0.02) in patients with FM compared to controls. Thresholds for pain evoked by electrical stimulation at the skin were not significantly different in the 2 groups. The pain threshold to repeated intramuscular stimulation was significantly (p = 0.02) lower for the patients with FM compared to the control group, indicating that the temporal nociceptive summation was more pronounced in patients with FM. This is an indication of central sensitization (hyperexcitability). Infusion of hypertonic saline evoked muscle pain with a longer duration (p = 0.01) in patients with FM, and referred pain that spread to a larger area (p = 0.002) than in controls. This is an indication of central hyperexcitability. CONCLUSION: There is a state of central hyperexcitability in the nociceptive system in FM. This hyperexcitability can be revealed by excitation of intramuscular nociceptors in a muscle with no spontaneous pain.

Adult↗
PubMed1997

Extradural catheter-related infections in patients with infected cutaneous wounds.

We report three previously healthy individuals, aged 19-40 yr, with co-existing infected lower limb cutaneous wounds, who developed, in all probability, spinal space infections complicating continuous extradural analgesia. As the number of patients with extradural catheters and large cutaneous wounds represents a small fraction of the total number of patients with extradural catheters, three cases of presumed spinal space infection over a 4-yr period suggests that extradural analgesia with a catheter technique in this clinical situation is unsafe.

Adult↗
PubMed1997

Report from the HLA class II typing by PCR-SSP Multicentre Study.

Results from 360 HLA-DR and -DQ 'low-resolution' typings with polymerase chain reaction sequence-specific primers (PCR-SSP), performed by nine laboratories, were analysed for their overall utility in routinely defining the HLA-DR1-DR18, DR51-DR53 and DQ1-DQ9 specificities in less than 2.5 h. Thirty EDTA blood samples and 10 DNA samples were distributed and analysed by each laboratory. DNA was extracted using a rapid bromide salt extraction protocol. Complete HLA-DR and -DQ typings were performed, three by three, on pre-aliquoted 96-tube PCR trays. When compared with reference typing, 351/360 (98%) correct DR typings were obtained, whereas 320/360 (89%) of the DQ phenotypes were correctly assigned. The time for three complete HLA-DR and -DQ 'low-resolution' typings, including DNA extraction, ranged from 2.0 h to 2.3 h. Unfortunately, an unusually high level of PCR amplification failures was observed (3%), probably due to diffusion and a significant volume loss from some of the pre-aliquoted primer mixes. Consequently, only 52% of the typings were without any amplification failure, and 0-2 amplification failures where found in 88% of the PCR-SSP typings performed. The number of HLA-DR-DQ retypings needed was 7 and 8%, respectively, reflecting the low number of typings where allelic identification was directly affected by the relatively high level of amplification failures in this study. Thus, a 91-98% success rate of correctly identified HLA-DR and -DQ alleles could be maintained, even under suboptimal typing conditions.

Alleles↗