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Biomedical subjects

A Mårtensson

Publications and source records attributed to A Mårtensson.

At least 19 recordsLinked to original sources
PubMed1999

Lymphoid-restricted development from multipotent candidate murine stem cells: distinct and complimentary functions of the c-kit and flt3-ligands.

The two tyrosine kinase receptors, c-kit and flt3, and their respective ligands KL and FL, have been demonstrated to play key and nonredundant roles in regulating the earliest events in hematopoiesis. However, their precise roles and potential interactions in promoting early lymphoid commitment and development remain unclear. Here we show that most if not all murine Lin(-/lo)Sca1(+)c-kit(+) bone marrow (BM) cells generating B220(+)CD19(+) proB-cells in response to FL and interleukin-7 (IL-7) also have a myeloid potential. In contrast to FL + IL-7, KL + IL-7 could not promote proB-cell formation from Lin(-/lo)Sca1(+)c-kit(+) cells. However, KL potently enhanced FL + IL-7-stimulated proB-cell formation, in part through enhanced recruitment of FL + IL-7-unresponsive Lin(-/lo)Sca1(+)c-kit(+) progenitors, and in part by enhancing the growth of proB-cells. The enhanced recruitment (4-fold) in response to KL occurred exclusively from the Lin(-/lo)Sca1(+)c-kit(+)flt3(-) long-term repopulating stem cell population, whereas KL had no effect on FL + IL-7-stimulated recruitment of Lin(-/lo)Sca1(+)c-kit(+)flt3(+) short-term repopulating cells. The progeny of FL + IL-7-stimulated Lin(-/lo)Sca1(+)c-kit(+) cells lacked in vitro and in vivo myeloid potential, but efficiently reconstituted both B and T lymphopoiesis. In agreement with this FL, but not KL, efficiently induced expression of B220 and IL-7 receptor-alpha on Lin(-/lo)Sca1(+)c-kit(+)flt3(+) cells. Thus, whereas KL appears crucial for recruitment of FL + IL-7-unresponsive candidate (c-kit(+)flt3(-)) murine stem cells, FL is essential and sufficient for development toward lymphoid restricted progenitors from a population of (c-kit(+)flt3(+)) multipotent short-term reconstituting progenitors.

Animals↗
PubMed1999

Spi-C, a novel Ets protein that is temporally regulated during B lymphocyte development.

A novel Ets protein was isolated by yeast one-hybrid screening of a cDNA library made from lipopolysaccharide-stimulated mouse splenic B cells, using the SP6 kappa promoter kappaY element as a bait. The novel Ets protein was most closely related to PU.1 and Spi-B within the DNA binding Ets domain and was therefore named Spi-C. However, Spi-C may represent a novel subgroup within the Ets protein family, as it differed significantly from Spi-B and PU.1 within helix 1 of the Ets domain. Spi-C was encoded by a single-copy gene that was mapped to chromosome 10, region C. Spi-C interacted with DNA similarly to PU.1 as judged by methylation interference, band-shift and site selection analysis, and activated transcription of a kappaY element reporter gene upon co-transfection of HeLa cells. Spi-C RNA was expressed in mature B lymphocytes and at lower levels in macrophages. Furthermore, pre-B cell and plasma cell lines were Spi-C-negative, suggesting that Spi-C might be a regulatory molecule during a specific phase of B lymphoid development.

Amino Acid Sequence↗
PubMed1999

Partial block in B lymphocyte development at the transition into the pre-B cell receptor stage in Vpre-B1-deficient mice.

The surrogate light chain (SL) is composed of two polypeptides, Vpre-B and lambda5. In large pre-BII cells the SL chain associates with Ig mu heavy chain (muH) to form the pre-B cell receptor (pre-BCR). In mice there are two Vpre-B genes which are 98% identical within the coding regions. The two genes are co-expressed at the RNA level and encode functional proteins that can assemble with lambda5. However, it is not known whether both gene products serve the same function in vivo. Here we have established mice that lack the Vpre-B1 gene (VpreB1(-/-)), but still express the Vpre-B2 gene, both as RNA and protein. In Vpre-B1(-/-) mice, the bone marrow cellularity and the percentage of B220+ cells is normal. However, among the B220+ cells, the percentage of pre-BI cells is increased, and the percentage of pre-BII and immature B cells is slightly decreased, suggesting that the lack of Vpre-B1 causes a partial block at the transition from pre-BI to pre-BII cells, i.e. into the pre-BCR stage. The number of cells that produce a functional pre-BCR is thus lower, but the cells that reach this stage are normal as they can be expanded by proliferation and then differentiate into more mature cells. The spleens of Vpre-B1 homozygous mutant mice show normal numbers of B and T lymphocytes. Moreover, the Ig loci are allelicly excluded and the homozygous mutant mice respond with normal levels of antigen-specific antibodies to T-dependent antigens. These results demonstrate that VpreB2 alone is capable of supporting B lymphocyte development in the bone marrow and can give rise to immuno-competent cells in the periphery.

Animals↗
PubMed1998

Identification of a tissue- and differentiation stage-specific enhancer of the VpreB1 gene.

The VpreB and lambda 5 genes encode proteins that associate non-covalently to form the so-called surrogate light (SL) chain. The SL chain complexes with the immunoglobulin heavy chain to form the pre-B cell receptor, which plays a critical role in B cell development. Expression of the murine SL genes is regulated at the level of transcription initiation. Here, we show that a VpreB1 enhancer is located within the 356 bp immediately upstream of the coding sequence. Interestingly, this region exhibits 96% identity to the upstream region of VpreB2. Deletion mapping located the enhancer to between positions -214 and -47 (+1 is the 5'-most transcription initiation site). The enhancer is tissue and differentiation stage specific, and is composed of several DNA elements that are important for its activity. We also show that a transcription factor, early B cell factor, binds to two such elements, and that at least one of these sites is involved in determining enhancer activity.

Animals↗
PubMed1998

Bacteraemic pneumococcal infections in Southern Sweden 1981-96: trends in incidence, mortality, age-distribution, serogroups and penicillin-resistance.

In a survey of pneumococcal blood isolates from patients in Southern Sweden, 560 isolates were found between 1981 and 1996. Between these years, the incidence of pneumococcal bacteraemia increased from 5.2 to 15.2/100,000/y. The eight most common serogroups/types (14, 7, 9, 6, 23, 3, 4 and 19) accounted for > 75% of the isolates, and 96.4% of the isolates were of serogroups/types represented in the present vaccine. A male preponderance (1.17:1) was noted, and the men were younger than the women (mean 57 vs 63 y of age; p < 0.05). The overall case-fatality rate during the period was 19%. Seven isolates with reduced susceptibility to penicillin were noted, all from 1991 to 1996. The increasing incidence of pneumococcal bacteraemia could not be explained by any of the following factors; age or sex of the patients, changes in prevailing serogroups/types, variations in vaccine use, emergence of penicillin-resistance, more liberal indications for blood cultures or improved culture methods.

Adolescent↗
PubMed1997

Early B cell factor binds to a site critical for lambda5 core enhancer activity.

The pre-B cell-specific expression of the lambda5 gene is regulated at the level of transcription. The 5' region of the lambda5 gene has been shown to contain an enhancer that activates heterologous promoters. Here, we show that this enhancer, B(lambda5), also acts as a lineage- and tissue-restricted enhancer on its own promoter. We define the enhancer core, b(lambda5), that carries around 50% of the total enhancer activity. We also demonstrate that the transcription factor early B cell factor (EBF) binds to a DNA motif in the lambda5 core enhancer which is crucial for enhancer activity, suggesting that lambda5 is a second target gene of EBF.

Animals↗
PubMed1997

Influences of muscle stretch reflexes on voluntary, velocity-controlled movements in spastic paraparesis.

We studied voluntary, velocity-controlled knee movements in 22 patients with spastic paraparesis (11 male, 11 female) and 22 healthy controls (11 male, 11 female). Torque and EMG activity of the quadriceps and the hamstring muscles were determined in maximal voluntary concentric (shortening) and eccentric (lengthening) actions of knee extensor and flexor muscles at constant movement velocities of 30, 60, 120 and 180 degrees/s, using an active, isokinetic dynamometer. In the spastic patients, the voluntary strength and the agonist EMG activity were reduced in all movements. The reduction was largest in concentric actions at high velocity. The antagonist EMG activity was reduced in the same proportion as the agonist EMG activity in eccentric actions. In concentric actions when stretch is imposed upon antagonists, the antagonist EMG activity increased with the velocity of stretch, indicating stretch reflex activation. In parallel with the stretch reflex activation of antagonists, there was reduced activation of the agonists compatible with Ia reciprocal inhibition of agonist motoneurons. When agonists were stretched in eccentric actions, stretch reflexes appeared to support the voluntary, agonist activation of knee flexor muscles but not knee extensors.

Adult↗
PubMed1996

A new device combining laser Doppler perfusion imaging and digital photography.

We describe a new method for acquisition and analysis of skin perfusion images acquired by laser Doppler scanning and digital photographs of the area scanned. Photographs are obtained with a commercial digital still video camera. A commercial software package is used to handle the perfusion image file and the digital photo. We describe software developed to assess blood flow distribution in detail in relation to the visual appearance of the skin, palpatory findings and other clinical signs. Possible clinical applications of the method described by case reports are post-operative evaluation of vascularized grafts and monitoring of treatment of chronic skin ulcers.

Blood Flow Velocity↗
PubMed1993

Long-term results of recurrent laryngeal nerve resection for adductor spasmodic dysphonia.

From a total of 43 adductor spasmodic patients over a 10-year period, 11 underwent resection of a portion of the recurrent laryngeal nerve on one side. The initial results were excellent but a varying degree of recurrence took place in 8 patients. In 4, a reoperation was done. At the final follow-up, 2-8 years after the primary operation, 4 patients were no longer suffering from spasmodic dysphonia, another 5 were better off than before surgery, and 1 remained unchanged. Only 1 was worse off. Electromyographic findings indicated that the recurrence of symptoms was due to regeneration of the nerve fibers.

Adult↗
PubMed1985

Isokinetic measurements of muscle strength in hysterical paresis.

The torque during isokinetic knee extensions and flexions was determined in repeated tests at 3 speeds of angular rotation in 25 patients with pareses considered to be hysterical after relevant examinations and follow-up. The torque records were combined with surface EMG from the quadriceps and the hamstring muscles in some patients. Besides the weakness, 3 signs were observed that are not usually seen in patients with pareses due to verified peripheral or central lesions. These signs were: Enlarged variability of torque in repeated tests of the same movement (larger than 20% of maximum torque in 22 patients). Higher torque in fast movements than in slow movements (8 patients). Force production in knee flexion less than that expected from the weight of leg and lever arm due to restraining activation of the quadriceps muscle (12 patients). The restraint was present although there was no spasticity. The signs reflect inconsistent and contradictory motor performance that is not compatible with a genuine paresis. Thus, they aid the identification of weakness of functional origin.

Adult↗
PubMed1982

Antiparetic and antispastic effects induced by tizanidine in patients with spastic paresis.

The effects of tizanidine were studied in patients with spastic paresis. The study consisted of 4 parts: I, double-blind cross-over trial at maximal dosage 10 mg/day in 13 patients; II, open trial at maximal dosage 32 mg/day in 10 patients; III, long-term medication at dosage 32 mg/day for 6-15 months in 4 patients; IV, single dose (12 mg) administration in 3 patients. The effects were evaluated from clinical examinations, subjective assessments, EMG, gait analysis and quantitative determinations of passive resistance and voluntary strength in isokinetic extensions and flexions of the knee and plantar and dorsal flexions of the ankle at different speeds of motion. At 3-10 mg/day, no effects were observed except for increased prime mover EMG activity in voluntary knee flexions. At 12-32 mg/day, passive resistance decreased significantly in 3 of the movements tested. The maximal voluntary strength increased significantly in 3 movements, frequently associated with enlarged activation of prime mover muscles, less frequently with reduced antagonist co-activation. Functional disability was subjectively reduced and verified by improved gait capacity in 4 patients. Sustained effects on motor performance during long-term medication were verified by withdrawal in 3 patients. Single dose administration resulted in reduced passive resistance and increased voluntary strength, associated with an increased activation of the prime mover muscles. The results indicate that tizanidine exerts its effects in part by reducing spastic restraint, in part by enhancing the capacity to activate paretic muscles.

Adult↗