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L Carlsson

Publications and source records attributed to L Carlsson.

At least 19 recordsLinked to original sources
PubMed1998

Expression of the LIM-homeobox gene LH2 generates immortalized steel factor-dependent multipotent hematopoietic precursors.

The genes controlling self-renewal and differentiation in the hematopoietic system are largely unknown. The LIM-homeobox genes are known to be important for asymmetric cell divisions and differentiation of specific cell types and organs. One member of this family, LH2, is expressed in fetal liver at the time of active hematopoiesis. Therefore, we have assessed the function of LH2 during the formation and initial expansion of the hematopoietic system by differentiating LH2-transduced embryonic stem (ES) cells in vitro. This procedure generated multipotent hematopoietic precursor cell (HPC) lines that required Steel factor for growth. HPC lines have been maintained in an undifferentiated state in culture for >7 months. Other growth factors tested efficiently induce terminal differentiation of HPCs into various mature myeloid lineages. Steel factor is also required and acts synergistically with the other growth factors to generate multilineage colonies from the HPCs. These HPC lines express transcription factors that are consistent with an immature progenitor, and the pattern of cell surface marker expression is similar to that of early fetal multipotent hematopoietic progenitors. Collectively, these data suggest that the HPC lines represent an early fetal multipotent hematopoietic progenitor, and suggest a role for LH2 in the control of cell fate decision and/or proliferation in the hematopoietic system.

Animals↗
PubMed1998

Biomechanical characterization of osseointegration: an experimental in vivo investigation in the beagle dog.

This study reports the results of torsion tests, pull-out tests, and lateral loading tests on osseointegrated commercially pure titanium fixtures. The tests were performed in vivo on six beagle dogs. Three fixtures, each with a diameter of 3.7 mm, were installed bilaterally in the tibia of each animal. The mean maximal pull-out load was 1.55 kN (n = 4), the mean maximal lateral transverse load was 0.21 kN (n = 2), the mean maximal lateral axial load was 0.18 kN (n = 2), the mean breakpoint torque was 0.31 Nm (n = 3), and the mean maximal torque was 0.43 Nm (n = 3). The torsion test revealed an almost immediate plastic deformation of the interface between the implant and bone; this indicates that although the contact between the bone and the implant is close, there is no strong bond, at least not in shear. The major transfer of load from the implant to the surrounding bone tissue must therefore depend on the design of the implant. A histological evaluation with measurements of the amount of bone in contact with the fixtures was performed. By the use of the histological and mechanical data, it is possible to estimate shear stresses in bone tissue (pull-out test) and in the interface (torque test). The mean maximal shear stress in bone tissue in the pull-out tests was 100 MPa (n = 4); the mean shear stress in the interface was 4.3 MPa (n = 3) in the torsion tests at the breakpoint torque and was 6.0 MPa (n = 3) at the maximal torque. It was also possible to estimate the shear modulus of elasticity in the pull-out and torque tests. The mean shear modulus in pull-out was 119 MPa (n = 4), and the mean apparent shear modulus in torsion was 9 kPa (n = 3) for an assumed interface thickness of 100 nm and was 86 kPa (n = 3) for an assumed interface thickness of 1,000 nm.

Animals↗
PubMed1998

Ceramic coating improves tibial component fixation in total knee arthroplasty.

Forty uncemented total knee arthroplasties (36 patients) were randomly allocated to a Miller-Galante II prosthesis with or without hydroxyapatite/tricalcium phosphate (HA/TCP) coating on the titanium fiber mesh on the undersurface of the tibial component. The patients were followed for 2 years with repeated radiostereometric examinations. After 2 years, the HA/TCP tibial components displayed smaller anterior-posterior tilt and less subsidence. The mean value of maximal total point motion was small: 0.5 mm in both groups. At 24 months, there were more radiolucent lines under the tibial tray and around the stem in the uncoated group, but the clinical results did not differ. HA/TCP coating on the undersurface of the tibial component improved the stability and seemed to improve the quality of the interface between the tibial component and the bone.

Aged↗
PubMed1998

Identification of a fetal hematopoietic precursor with B cell, T cell, and macrophage potential.

Despite years of investigation, precursor-progeny relationships within the developing lymphoid lineages of the hematopoietic system remain poorly defined. We have characterized the potential of precursors found within a subpopulation of fetal liver defined by AA4.1 and Fc gammaRII/III expression and predominantly restricted to lymphoid and macrophage development. When cultured in methylcellulose with appropriate cytokines, AA4.1+/Fc gammaR+ precursors generate colonies consisting of various lineages, including the combination of B cell, T cell, and macrophage. Retroviral marking studies showed that the lymphoid cells and macrophages within these colonies arise from a common precursor. These results demonstrate the presence of a common precursor with B cell-, T cell-, and macrophage-restricted potential and as such define an early restriction point within the fetal lymphoid system.

Animals↗
PubMed1998

Hormonal regulation of liver fatty acid-binding protein in vivo and in vitro: effects of growth hormone and insulin.

Liver fatty acid-binding protein (LFABP) is an abundant protein in hepatocytes that binds most of the long chain fatty acids present in the cytosol. It is suggested to be of importance for fatty acid uptake and utilization in the hepatocyte. In the present study, the effects of bovine GH (bGH) and other hormones on the expression of LFABP and its messenger RNA (mRNA) were studied in hypophysectomized rats and in vitro using primary cultures of rat hepatocytes. One injection of bGH increased LFABP mRNA levels about 5-fold after 6 h, but there was no effect of this treatment on LFABP levels. However, 7 days of bGH treatment increased both LFABP mRNA and LFABP protein levels 2- to 5-fold. Female rats had higher levels of LFABP than male rats. Hypophysectomy of female rats, but not that of male rats, decreased LFABP levels markedly. Treatment of hypophysectomized rats with bGH for 7 days as two daily injections or as a continuous infusion increased LFABP levels to a similar degree. This finding indicates that the sex difference in the expression of LFABP is not regulated by the sexually dimorphic secretory pattern of GH. Neither insulin nor insulin-like growth factor I treatment of hypophysectomized rats for 6-7 days had any effect on LFABP mRNA or LFABP levels. In vitro, bGH dose-dependently increased the expression of LFABP mRNA, but only in the presence of insulin. Insulin alone had a marked dose-dependent effect on LFABP mRNA levels and was of importance for maintaining the expression of LFABP mRNA during the culture. Incubation with bGH increased LFABP mRNA levels within 3 h. GH had no effect on LFABP mRNA levels in the presence of actinomycin D, indicating a transcriptional effect of GH. Incubation with glucagon in vitro decreased LFABP mRNA levels markedly, indicating that glucagon, in contrast to GH, has an effect opposite that of insulin on LFABP mRNA expression. It is concluded that GH is an important regulator of LFABP in vivo and in vitro. In contrast to the effect of GH on insulin-like growth factor I mRNA, the presence of insulin was a prerequisite for the effect of GH on LFABP mRNA expression in vitro. The results emphasize the role of GH in the regulation of hepatic fatty acid metabolism.

Animals↗
PubMed1998

Leptin levels in protracted critical illness: effects of growth hormone-secretagogues and thyrotropin-releasing hormone.

Prolonged critical illness is characterized by feeding-resistant wasting of protein, whereas reesterification, instead of oxidation of fatty acids, allows fat stores to accrue and associate with a low-activity status of the somatotropic and thyrotropic axis, which seems to be partly of hypothalamic origin. To further unravel this paradoxical metabolic condition, and in search of potential therapeutic strategies, we measured serum concentrations of leptin; studied the relationship with body mass index, insulin, cortisol, thyroid hormones, and somatomedins; and documented the effects of hypothalamic releasing factors, in particular, GH-secretagogues and TRH. Twenty adults, critically ill for several weeks and supported with normocaloric, continuously administered parenteral and/or enteral feeding, were studied for 45 h. They had been randomized to receive one of three combinations of peptide infusions, in random order: TRH (one day) and placebo (other day); TRH + GH-releasing peptide (GHRP)-2 and GHRP-2; TRH + GHRH + GHRP-2 and GHRH + GHRP-2. Peptide infusions were started after a 1-microgram/kg bolus at 0900 h and infused (1 microgram/kg.h) until 0600 h the next morning. Serum concentrations of leptin, insulin, cortisol, T4, T3, insulin-like growth factor (IGF)-I, IGF-binding protein-3 and the acid-labile subunit (ALS) were measured at 0900 h, 2100 h, and 0600 h on each of the 2 study days. Baseline leptin levels (mean +/- SEM: 12.4 +/- 2.1 micrograms/L) were independent of body mass index (25 +/- 1 kg/m2), insulin (18.6 +/- 2.9 microIU/mL), cortisol (504 +/- 43 mmol/L), and thyroid hormones (T4: 63 +/- 5 nmol/L, T3: 0.72 +/- 0.08 nmol/L) but correlated positively with circulating levels of IGF-I [86 +/- 6 micrograms/L, determination coefficient (R2) = 0.25] and ALS (7.2 +/- 0.6 mg/L, R2 = 0.32). Infusion of placebo or TRH had no effect on leptin. In contrast, GH-secretagogues elevated leptin levels within 12 h. Infusion of GHRP-2 alone induced a maximal leptin increase of +87% after 24 h, whereas GHRH + GHRP-2 elevated leptin by up to +157% after 24 h. The increase in leptin within 12 h was related (R2 = 0.58) to the substantial rise in insulin. After 45 h, and having reached a plateau, leptin was related to the increased IGF-I (R2 = 0.37). In conclusion, circulating leptin levels during protracted critical illness were linked to the activity state of the GH/IGF-I axis. Stimulating the GH/IGF-I axis with GH-secretagogues increased leptin levels within 12 h. Because leptin may stimulate oxidation of fatty acids, and because GH, IGF-I, and insulin have a protein-sparing effect, GH-secretagogue administration may be expected to result in increased utilization of fat as preferential substrate and to restore protein content in vital tissues and, consequently, has potential as a strategy to reverse the paradoxical metabolic condition of protracted critical illness.

Adult↗
PubMed1998

Low growth hormone secretion in patients with fibromyalgia--a preliminary report on 10 patients and 10 controls.

OBJECTIVE: To evaluate the secretion of growth hormone in patients with fibromyalgia (FM). METHODS: Serum concentrations of growth hormone (24 h profiles), insulin-like growth factor I (IGF), and IGF binding protein-3 were determined in 10 women with FM and in 10 healthy controls. Quality of sleep was assessed by means of a visual analog scale. RESULTS: Sleep was significantly more disturbed in the patients than in controls. A significantly lower secretion of growth hormone was found in the patients in comparison with healthy controls. CONCLUSION: These results suggest that growth hormone secretion is decreased in patients with FM. Substitution therapy with low doses of growth hormone may be worth evaluating in the treatment of FM.

Adult↗
PubMed1997

Desmin is essential for the tensile strength and integrity of myofibrils but not for myogenic commitment, differentiation, and fusion of skeletal muscle.

A null mutation was introduced into the mouse desmin gene by homologous recombination. The desmin knockout mice (Des -/-) develop normally and are fertile. However, defects were observed after birth in skeletal, smooth, and cardiac muscles (Li, Z., E. Colucci-Guyon, M. Pincon-Raymond, M. Mericskay, S. Pournin, D. Paulin, and C. Babinet. 1996. Dev. Biol. 175:362-366; Milner, D.J., G. Weitzer, D. Tran, A. Bradley, and Y. Capetanaki. 1996. J. Cell Biol. 134:1255- 1270). In the present study we have carried out a detailed analysis of somitogenesis, muscle formation, maturation, degeneration, and regeneration in Des -/- mice. Our results demonstrate that all early stages of muscle differentiation and cell fusion occur normally. However, after birth, modifications were observed essentially in weight-bearing muscles such as the soleus or continually used muscles such as the diaphragm and the heart. In the absence of desmin, mice were weaker and fatigued more easily. The lack of desmin renders these fibers more susceptible to damage during contraction. We observed a process of degeneration of myofibers, accompanied by macrophage infiltration, and followed by a process of regeneration. These cycles of degeneration and regeneration resulted in a relative increase in slow myosin heavy chain (MHC) and decrease in fast MHC. Interestingly, this second wave of myofibrillogenesis during regeneration was often aberrant and showed signs of disorganization. Subsarcolemmal accumulation of mitochondria were also observed in these muscles. The lack of desmin was not compensated by an upregulation of vimentin in these mice either during development or regeneration. Absence of desmin filaments within the sarcomere does not interfere with primary muscle formation or regeneration. However, myofibrillogenesis in regenerating fibers is often abortive, indicating that desmin may be implicated in this repair process. The results presented here show that desmin is essential to maintain the structural integrity of highly solicited skeletal muscle.

Adenosine Triphosphatases↗
PubMed1997

A potential role of R-cadherin in striated muscle formation.

We have examined the murine embryonic expression pattern of the cell adhesion molecule R-cadherin in muscle, kidney, thymus, and lung. In developing muscle, R-cadherin was first seen at 10.5-11.5 days postcoitum in the somitic myotome. Consistently, we found R-cadherin expressed at the highest levels in the myotome, early skeletal muscle, and smooth muscle (both vascular and visceral), while very low levels of R-cadherin were detected in the heart. The expression pattern and subcellular localization of R-cadherin in developing skeletal muscle indicate a possible role in myoblast cell-cell interactions during both primary and secondary myogenesis. In the developing kidney, R-cadherin was first detected at 10.5 days postcoitum in the mesonephric epithelial tubule cells. In the metanephric kidney, it was specifically expressed in the pretubular aggregates, comma- and S-shaped bodies, proximal tubules, and collecting ducts. Thus, in the kidney, R-cadherin was associated with the mesenchymal-epithelial transition. R-cadherin was also found in other developing epithelia, for example in the thymic epithelial cells. In the lung, R-cadherin was expressed at the highest levels in the smooth muscle surrounding the lung epithelial tubules. To test whether R-cadherin can direct formation of tissues, we constitutively expressed R-cadherin in E-cadherin-/- ES cells and examined histogenesis in teratomas derived from these cells. R-cadherin exclusively rescued formation of striated muscle and epithelia in the teratomas. R-cadherin's ability to form epithelia in vivo was substantiated by its ability to rescue formation of cystic embryoid bodies in vitro. By comparing our data with the previously reported embryonic expression patterns and histogenetic activities of E- and N-cadherin, we suggest that R-cadherin plays an important role in the formation of striated muscle and possibly also of epithelia.

Animals↗
PubMed1997

Targeted disruption of the V(H) 81X gene: influence on the B cell repertoire.

We have generated a mutant mouse in which the most D-proximal V(H) gene (V(H)81X) has been disrupted by introducing a neomycin-resistance gene into the V(H)81X exon by means of gene targeting in embryonic stem cells. The mutant mice generated are unable to express the V(H)81X gene but appear to display a normal pattern of B cell differentiation as well as normal numbers of bone marrow and peripheral B cells from fetal life all through ontogeny. They mount normal immune responses to several different antigens tested. In contrast, the distribution of V(H) gene rearrangements in the V(H)7183 family is altered in homozygous mutant mice. Thus, the antibody repertoire of the targeted mice is modified, at least as far as the expression of V(H)7183 genes is concerned.

Animals↗
PubMed1997

Null mutation in the desmin gene gives rise to a cardiomyopathy.

A null mutation in the desmin gene has been introduced into the germ line of mice. Such mice develop and reproduce normally proving that desmin is not needed either for the formation of the heart or the alignment of functioning myofibrils. However, cardiovascular lesions and a skeletal myopathy were observed in growing and adult mice. In the present study we have carried out a detailed analysis of these cardiac lesions. Homozygous mutant mice, which were confirmed to lack expression of desmin mRNA and desmin protein in the heart, were revealed by electron microscopy to contain degenerating cardiomyocytes as early as 5 days post-partum. At 10 days post-partum and onwards the degeneration of cardiomyocytes gave rise to areas with an accumulation of macrophages, fibrosis and calcification preferentially in the inter-ventricular septum and the free wall of the right ventricle. The localization of the lesions mainly to these sites suggested that it is not the work load and contractions per se which were the pathogenic events leading to the cardiomyopathy. It might be that stress related to lengthening of the myocytes occur more in the right ventricle than in the left. At the ultrastructural level changes in the intercalated discs, disruption of the sarcolemma and supercontraction of myofibrils seemed to be the key events leading to cardiomyocyte death. Thus, the intermediate filaments are required to maintain the basic integrity of cardiomyocytes and especially the link between the intermediate filaments and the sarcolemma appear more important than previously realized.

Animals↗
PubMed1997

Clinical and radiologic survivorship of cementless tibial components fixed with finned polyethylene pegs.

One hundred twenty patients (22 men, 98 women; 144 knees) with uncemented Freeman-Samuelson total knee arthroplasty were followed prospectively. Eighty-one patients had rheumatoid arthritis and 39 patients had osteoarthrosis. The mean follow-up period was 6.8 years. Three different types of tibial components were used: a high-density polyethylene component without stem, a metal-backed tibial component without stem, and a metal-backed tibial component with stem. Progressive varus tilting turned out to be an early sign of failure and occurred in 22% of the tibial components. Revision of the tibial component was done in 17 knees. Survival analysis with revision as endpoint revealed a survival rate of 79% at a follow-up period of 10 years. Cementless fixation of this design using macrointerlocking pegs and no other stabilization resulted in poor fixation and a high revision rate and cannot be recommended.

Adult↗
PubMed1997

Postoperative inflammatory response after autologous and allogeneic blood transfusion.

BACKGROUND: Allogeneic blood transfusions cause immunosuppression. The aim of this study was to determine whether complement anaphylatoxins, cytokines, or both are released in the recipient, after blood transfusions in general, and after autologous blood transfusions in particular. METHODS: Thirty-one patients having total hip joint replacement surgery were randomized to receive either allogeneic red blood cells (n = 15) or predeposited autologous whole blood transfusion (n = 16). Plasma concentrations of the anaphylatoxins C3a and C5a, the terminal C5b-9 complement complex, and cytokines IL-6 and IL-8 in the recipients were repeatedly analyzed before, during, and after surgery. RESULTS: Significantly increased concentrations of IL-6 and IL-8 appeared in both groups, with a significantly greater increase in the autologous blood group. Patients in both groups developed a moderate but significant increase of C3a without a significant difference between them. C5a and terminal C5b-9 complement complex were not greatly changed. CONCLUSIONS: The study showed a greater increase in cytokine concentration after autologous blood transfusion than after allogeneic blood transfusion. The lower response in the latter may result from transfusion-induced suppression of cellular immunity.

Adult↗
PubMed1997

Myringotomized mice develop myringosclerosis in the pars flaccida and not in the pars tensa.

The development of myringosclerosis has been correlated with increased production of oxygen-derived free radicals. For the present study, we used a null mutant mouse lacking extracellular superoxide dismutase to test the hypothesis that increased production of free radicals can cause the development of myringosclerosis. Null mutant mice and wild-type, control mice were myringotomized and kept in ambient air for 3 weeks. Both groups developed myringosclerosis in the pars flaccida, but not in the pars tensa. The sclerotic lesions were visible in both the light and the electron microscope but not in the otomicroscope. In particular, the localization of the sclerotic deposits was found beneath both the inner and outer epidermal epithelium. No difference concerning the extent or number of sclerotic lesions between the null mutant and the wild-type mice could be distinguished.

Animals↗
PubMed1997

A bone-anchored percutaneous connector system for neural prosthetic applications.

A percutaneous connector system has been developed for use in neural prosthetic applications. It is based on a skin-penetrating, bone-anchored titanium pedestal, housing an II-channel electrode array. Initial applications for the system are in audiology and as such, the proposed fixture site is in the temporal bone. The titanium pedestal is based on existing design features of the EPI Bioglass implant, developed by University College London (UCL), and the Brånemark System, employed by Nobel Biocare AB. The electrode array, consisting of platinum wires in a silicone carrier, can be custom designed to suit the application. The design features of the connector system are reviewed. Animal studies have been used to assess soft tissue reactions and the osseointegration of the pedestal. The histological data are presented. The pedestal, electrode array and the mating external connector are currently undergoing mechanical and electrical testing. The percutaneous connector system will undergo clinical trials, initially in the study of tinnitus (employing stimulation via an extracochlear electrode), and as part of a cochlear implant system (using a multichannel intracochlear electrode array and digital signal processing techniques.

Animals↗
PubMed1997

Growth hormone (GH) assays: influence of standard preparations, GH isoforms, assay characteristics, and GH-binding protein.

The impact of the adoption of the new biosynthetic growth hormone (GH) WHO International Reference Preparation (IRP 88/624), and the recommendation to report results in microgram/L instead of mU/L, is described. Conversion factors were determined by comparing both the linear and nonlinear relations of the GH values. The Pharmacia polyclonal IRMA (p-IRMA) and the DELFIA monoclonal time-resolved immunofluorometric assay (trIFMA) with kit calibrators calibrated either against the pituitary-derived WHO IRP 80/505 or the new 88/624 were evaluated. Conversion factors of 4.17 mU/L = 1 microgram/L for the p-IRMA and 4.31 mU/L = 1 microgram/L for the trIFMA were necessary. Different cross-reactivity patterns for the deaminated and dimer 22-kDa, 20-kDa, and 17-kDa GH isoforms were found. Expected GH recovery was similar when the measured values were adjusted according to the results of the cross-reactivity study.

Adolescent↗