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Biomedical subjects

A Lindahl

Publications and source records attributed to A Lindahl.

At least 19 recordsLinked to original sources
PubMed2006

In vivo MR imaging of magnetically labeled human embryonic stem cells.

INTRODUCTION: Human embryonic stem cells (hES) have emerged as a potentially new therapeutic approach for treatment of heart and other diseases applying the concept of regenerative medicine. A method for in vivo visualization and tracking of transplanted hES would increase our understanding of in vivo hES behavior in both experimental and clinical settings. The aim of this study was to evaluate the feasibility of magnetic labeling and visualization of hES with magnetic resonance imaging (MRI). METHODS: hES were established and expanded according to standard procedures. After expansion, the cells were cultured under feeder free conditions and magnetically labeled by addition of dextran-coated Ferrum-oxide particles (Endorem) to the medium. Accumulation of small particles of iron-oxide (SPIO) in hES was assessed by Prussian blue staining and electron microscopy. For in vitro MRI, the labeled and unlabeled hES were examined in cell solution and after transplantation into explanted mouse heart ( approximately 100,000 cells) on a Bruker Avance DMX 500 vertical magnet at 11.75 T. A multi-slice, multi spin-echo T(2)-weighted images were obtained. For in vivo imaging, the experiments were performed on male Sprague-Dawley using Bruker Biospec 2.35 T magnet. The hES were directly injected ( approximately 500,000 cells) after surgical procedure (thoracotomy) into anterior left ventricular (LV) wall. Multi-slice T(2)-weighted gradient echo images were obtained using cardiac gating. RESULTS: hES appeared to be unaffected by magnetic labeling and maintained their ability to proliferate and differentiate. No additive agent for membrane permeabilisation was needed for facilitation of intracellular SPIO accumulation. Prussian blue and electron microscopy have revealed numerous iron particles in the cytoplasm of hES. On T(2)-weighted images, the labeled cells have shown well-defined hyopintense areas at the site of injection in anterior LV wall both in vitro and in vivo. CONCLUSIONS: It is feasible to magnetically label and visualize hES both in vitro and in vivo. MR visualization of magnetically labeled hES may be a valuable tool for in vivo tracking of hES.

Animals↗
PubMed2006

Immature porcine knee cartilage lesions show good healing with or without autologous chondrocyte transplantation.

OBJECTIVE: The purpose of this study was to find out how deep chondral lesions heal in growing animals spontaneously and after autologous chondrocyte transplantation. METHODS: A 6mm deep chondral lesion was created in the knee joints of 57 immature pigs and repaired with autologous chondrocyte transplantation covered with periosteum or muscle fascia, with periosteum only, or left untreated. After 3 and 12 months, the repair tissue was evaluated with International Cartilage Repair Society (ICRS) macroscopic grading, modified O'Driscoll histological scoring, and staining for collagen type II and hyaluronan, and with toluidine blue and safranin-O staining for glycosaminoglycans. The repair tissue structure was also examined with quantitative polarized light microscopy and indentation analysis of the cartilage stiffness. RESULTS: The ICRS grading indicated nearly normal repair tissue in 65% (10/17) after the autologous chondrocyte transplantation and 86% (7/8) after no repair at 3 months. At 1 year, the repair tissue was nearly normal in all cases in the spontaneous repair group and in 38% (3/8) in the chondrocyte transplantation group. In most cases, the cartilage repair tissue stained intensely for glycosaminoglycans and collagen type II indicating repair tissue with true constituents of articular cartilage. There was a statistical difference in the total histological scores at 3 months (P=0.028) with the best repair in the spontaneous repair group. A marked subchondral bone reaction, staining with toluidine blue and collagen type II, was seen in 65% of all animals. CONCLUSIONS: The spontaneous repair ability of full thickness cartilage defects of immature pigs is significant and periosteum or autologous chondrocytes do not bring any additional benefits to the repair.

Animals↗
PubMed2005

Clonal growth of human articular cartilage and the functional role of the periosteum in chondrogenesis.

OBJECTIVE: Clinical cartilage repair with transplantation of cultured chondrocytes, the first described technique introduced in 1994, includes a periosteal membrane but today cells are also implanted without the periosteal combination. The aim of this study was to see if the periosteum had more than a biomechanical function and if the periosteum had a biological effect on the seeded cells tested in an agarose system in which the clonal growth in agarose and the external growth stimulation could be analysed. METHODS: Four different experiments were used to study the growth of human chondrocytes in agarose and the periosteal influence. Human chondrocytes were isolated and transferred to either primary or secondary agarose culture. After 4 weeks, the total number of clones >50 microm was counted. Cocultures of chondrocytes and periosteal tissue, cultures of chondrocytes with conditioned medium from chondrocytes, periosteal cells and fibroblast were used to study a potential stimulatory effect on growth and different cytokines and growth factors were analysed. RESULTS: It was found that the human chondrocytes had different growth properties in agarose with the formation of four different types of clones: a homogenous clone without matrix production, a homogenous clone with matrix production, a differentiated clone with matrix production and finally a differentiated clone without matrix production. The periosteum exerted a paracrine effect on cultured chondrocytes in agarose resulting in a higher degree of cloning. The chondrocytes produced significant amounts of interleukin (IL)-6, IL-8, granulocyte-macrophage colony-stimulating factor (GM-CSF) and transforming growth factor (TGF)-beta. The periosteum produced significant amounts of IL-6, IL-8 and TGF-beta. Cocultures of chondrocytes and periosteum demonstrated a potentiation of IL-6 and IL-8 release but not of TGF-beta and GM-CSF. CONCLUSION: Articular chondrocytes are able to form clones of different properties in agarose and the periosteum has a capacity of stimulating chondrocyte clonal growth and differentiation and secretes significant amounts of IL-6, IL-8, GM-CSF and TGF-beta. It may be that the repair of cartilage defects with seeded chondrocytes could benefit from the combination with a periosteal graft. The production of TGF-beta by implanted chondrocytes could influence the chondrogenic cells in the periosteum to start a periosteal chondrogenesis and together with the matrix from implanted chondrocyte production, a repair of cartilaginous appearance may develop; a dual chondrogenic response is possible.

Adult↗
PubMed2005

Clonal populations of chondrocytes with progenitor properties identified within human articular cartilage.

The aim of the present study was to identify and characterize progenitor properties of human articular chondrocytes selected by using agarose suspension culture. In this chondrogenic selective culture condition, about 3.6% of seeded surplus chondrocytes from patients undergoing articular chondrocyte transplantation proliferated and formed cell clusters after 6 weeks. Phase-contrast microscopy and transmission electron microscopy revealed four different types of cell clusters differing in cellular content and matrix production. Based on their morphological features, they were named the homogenous (H), the homogenous matrix (HM), the differentiated matrix (DM) and the differentiated (D) cell clusters. All cell clusters showed positive safranin O staining, and matrix was positive for antibodies detecting type II collagen and aggrecan. The clusters were further demonstrated to express the genes for fibroblast growth factor receptor 3, type IIA collagen and type IIB collagen, while type X collagen was not expressed. After subcloning, the H and HM clusters demonstrated the best proliferative capacity. Chondrocytes from these two cell clusters also showed phenotypic plasticity in chondrogenic, adipogenic as well as osteogenic assays. This study demonstrates that existing subpopulations of cells with chondroprogenitor properties can be isolated from human adult articular cartilage using agarose suspension cultures.

Adolescent↗
PubMed2003

Subchondral bone reaction associated with chondral defect and attempted cartilage repair in goats.

Repair of cartilage damage with autologous chondrocyte transplantation (ACT) has become popular in clinical use during the past few years. Although clinical results have mostly been successful, several unanswered questions remain regarding the biological mechanism of the repair process. The aim of this study was to develop a goat model for ACT. The repair was not successful due to the graft delamination, but we characterize the subchondral changes seen after the procedure. A chondral lesion was created in 14 goat knees, operated on 1 month later with ACT, and covered with periosteum or a bioabsorbable poly-L/D-lactide scaffold. After 3 months, only two of the five lesions repaired with ACT showed partly hyaline-like repair tissue, and all lesions (n = 4) with the scaffold failed. Even though the lesions did not extend through the calcified cartilage, the bone volume and collagen organization of bone structure were decreased when assessed by quantitative polarized light microscopy. There was a significant loss of bone matrix and distortion of the trabecular structure of subchondral bone, which extended several millimeters into the bone. The subchondral bone demonstrated strong hyaluronan staining in the bone marrow and cartilaginous areas with signs of endochondral ossification, suggesting structural remodeling of the bone. The goat model used here proved not to be an optimal model for ACT. The changes in subchondral bone may alter the biomechanical properties of the subchondral plate and thus the long-term survival of the repair tissue after ACT.

Animals↗
PubMed2003

Phenotypic plasticity of human articular chondrocytes.

BACKGROUND: Progenitor cells in mesenchymal tissues are important in the maintenance of tissue homeostasis and regeneration capacity. Articular cartilage is a tissue with a very low capacity for repair. One explanation could be the lack of chondrogenic progenitor cells within the adult tissue. As a test of chondrogenic differentiation potential, we examined the ability of isolated chondrocytes to take on several phenotypic identities within the mesenchymal lineage by applying culture techniques and markers used in the study of the phenotypic plasticity of marrow-derived mesenchymal stem cells (MSCs). METHODS: Culture-expanded human articular chondrocytes were analyzed for chondrogenic, adipogenic, and osteogenic capacity in defined in vitro culture systems. The osteochondrogenic potential of cells loaded into porous calcium-phosphate ceramic cubes implanted into mice was also determined. RESULTS: The different assays demonstrated that culture-expanded chondrocytes have the potential to form cartilage in pellet mass cultures, to form adipose cells in dense monolayer cultures, and to form a calcium-rich matrix in an osteogenic assay. In the in vitro assays, a variability of phenotypic plasticity was demonstrated among the donors. In contrast with MSCs, chondrocytes formed cartilage only (and not bone) in the in vivo osteochondrogenic assay. CONCLUSIONS: These results suggest that, within articular cartilage, there are chondrogenic cells that exhibit a level of phenotypic plasticity that is comparable with that of MSCs. However, there was a difference in the expression of bone in the in vivo assay.

Adipose Tissue↗
PubMed2001

Changes in p14(ARF) do not play a primary role in human chondrosarcoma tissues.

The locus encoding the tumor suppressor p16 has been found to code for a second, different protein. This protein, p14(ARF), has been shown to protect p53 from degradation. Like p16, its gene is often altered in different cancers. In this study, the first unique exon, exon 1 beta, of p14(ARF), has been studied in 22 chondrosarcoma tissues using polymerase chain reaction, DNA sequencing and methylation-specific polymerase chain reaction. One chondrosarcoma was found to have exon 1 beta homozygously deleted, but neither mutations nor methylations were found in any of the chondrosarcomas. This indicates that genetic changes of p14(ARF) are a rare event in chondrosarcoma.

Base Sequence↗
PubMed2001

Health economics benefits following autologous chondrocyte transplantation for patients with focal chondral lesions of the knee.

Autologous chondrocyte transplantation (ACT) for the treatment of cartilage injuries has been in clinical use for several years. Since this new technique is potentially more costly and invasive than traditional conservative therapies, we evaluated the effect of ACT on clinical outcome, absenteeism, disability status, and total direct economic burden in 57 patients with full-thickness chondral lesions of the knee treated between 1987 and 1996. Patients graded good or excellent following ACT in the treatments groups were: femoral condyles (28/33), femoral condyles with anterior cruciate ligament (ACL) repair (5/5), osteochondritis dissecans (7/8), and patellar lesions (9/11). Pre-ACT, 57/57 patients were disabled and post-ACT (mean follow-up 7.3 years) 44/57 had no sickness, 10/57 had minor disability, and 1/57 was disabled. Two of the 57 patients suffered re-injury during the follow-up time. In the 10-year period prior to ACT, the average cost of absenteeism and surgery was SEK 982,457 ($ 122,807) and SEK 47,000 ($ 5,875), respectively, compared to the post-ACT period where both absenteeism and medical costs were dramatically reduced: SEK 9,508 ($ 1,189) and SEK 7,050 ($ 881), respectively. In conclusion, 49 of the 57 patients improved clinically as a result of the ACT treatment. A dramatic cost-saving effect was demonstrated over a projected 10-year period due to reduced absenteeism and disability.

Absenteeism↗
PubMed2001

[Risk factors for low back pain among 1.389 pupils in the 8th and 9th grade. An epidemiologic study].

INTRODUCTION: The aim of this study was to investigate the frequency and severity of low back pain (LBP) in 13-16-year-old pupils in relation to selected factors, such as anthropometry, physical activity, smoking, hypermobility, and tightness of hamstring muscles. METHODS: The study was designed as a cross-sectional questionnaire-based survey and all the pupils were examined by the school doctor for height, weight, mobility of joints, and general health status. RESULTS: The lifetime prevalence of non-specific LBP was 58.9% and the one-year prevalence was 50.8% with no differences between the sexes. Recurrent/continuous LBP in a moderate to severe degree was recorded in 19.4% of the school children (182 F, 88 M). This was positively correlated to a female gender, a BMI of more than 25 kg/square meter, competitive sports for boys, poor physical fitness, daily smoking, heavy jobs in leisure time, increased use of the health system, and reduced life quality. DISCUSSION: Stepwise logistic regression analysis indicates that a female gender, daily smoking, and heavy jobs are important associated factors for severe LBP in adolescents, with an observed probability of 46% if all factors are present. We do not know yet whether these factors have any causal importance for the development of severe LBP.

Adolescent↗
PubMed2001

Alterations in the regulatory pathway involving p16, pRb and cdk4 in human chondrosarcoma.

The G1 regulatory pathway involving p16, pRb and cdk4 in the cell cycle has been investigated in human chondrosarcoma. The protein expression of p16, pRb and cdk4 was analyzed by Western blot in cultured cells from eight chondrosarcomas and in two chondrosarcoma cell lines. Both cell lines and one other sample were negative for p16. Moreover, one of the cell lines was pRb-negative and showed a high expression of cdk4 as well. In the other cell line and in three other samples pRb of expected size were detected in addition to a shorter form of the protein. To further investigate the reasons for down-regulation of the p16 protein, the p16-coding gene CDKN2 was analyzed by polymerase chain reaction (PCR), methyl-specific PCR (MSP) and sequencing in all tumor samples as well as in corresponding tumor tissues from three of the samples. The p16-negative samples were all found to have homozygous deletion of CDKN2. Another sample showed partial gene methylation and a heterozygous position in codon 148 was detected in one sample. The same base substitution was also found in two of the tissue samples. Finally, cytogenetic analysis of the samples with homozygously deleted CDKN2 revealed multiple structural abnormalities in all three cases. In conclusion, the p16/pRb/cdk4 pathway may play an important role in the pathogenesis of some chondrosarcomas.

Bone Neoplasms↗
PubMed2001

Estimated prevalences of respiratory symptoms, asthma and chronic obstructive pulmonary disease related to detection rate in primary health care.

OBJECTIVE: To assess the prevalence of respiratory symptoms, asthma and chronic obstructive pulmonary disease (COPD), and to relate it to an estimated detection rate in primary health care. DESIGN: A two-staged study with a cross-sectional survey and a clinical validation. SETTING: The adult population of Värmland, a county in Sweden. SUBJECTS: 4814 persons completed the survey and 206 the confirmative validation study. MAIN OUTCOME MEASURES: Prevalence of respiratory symptoms, of asthma and COPD. RESULTS: More than 40% reported respiratory symptoms. Wheeze was reported by 8.0%, shortness of breath by 11.4% and sputum production by 14.1%. Smoking was more common among women than among men. The prevalence of asthma was 8.2% and COPD 2.1%. Of persons with asthma, 33% were estimated to be undiagnosed, 67% used medication and nearly 60% attended primary health care services. CONCLUSION: Respiratory symptoms as well as asthma were common in this study and equivalent to earlier findings. The difference between the epidemiologically estimated prevalence of asthma and the lower detection rate in primary health care can be explained by at least three factors: persons who did not seek any care, were underdiagnosed or attended other health care providers.

Adolescent↗
PubMed2001

Autologous chondrocytes used for articular cartilage repair: an update.

Articular cartilage in adults has a poor ability to self-repair after a substantial injury; however, it is not known whether there is a cartilage resurfacing technique superior to the existing techniques. It is not satisfactory that at the beginning of the new millennium, there still is a lack of randomized studies comparing different cartilage repair techniques and there still is little knowledge of the natural course of a cartilaginous lesion. To date, various articular cartilage resurfacing techniques have the potential to improve the repair of cartilage defects and reduce the patient's disability. One such cartilage repair technique is autologous chondrocyte transplantation combined with a periosteal graft. Since the first patient was operated on in 1987, much interest in cartilage repair and cell engineering has emerged. The experience with autologous chondrocyte transplantation during the past 13 years with in vitro chondrocyte expansion, cartilage harvest, and postoperative biopsy technique is discussed, and the latest followup of 213 consecutive patients in different subgroups with 2 to 10 years followup is presented. The technique gives stable long-term results with a high percentage of good to excellent results (84%-90%) in patients with different types of single femoral condyle lesions, whereas patients with other types of lesions have a lower degree of success (mean, 74%).

Adult↗
PubMed2000

Changes of the p16 gene but not the p53 gene in human chondrosarcoma tissues.

The role of two important tumour suppressor genes, p16 and p53, was evaluated in cartilaginous tumour tissues. Genomic DNA from 22 chondrosarcomas, 5 benign chondroid tumours, 1 sample of reactive proliferative cartilage and 2 samples of normal cartilage were analysed using polymerase chain reaction, single strand conformational polymorphism, DNA sequencing and methylation-specific polymerase chain reaction. The p16 gene was found to be partly methylated in 5 high-grade chondrosarcomas and homozygously deleted in 1 chondrosarcoma. Moreover, a polymorphism was detected in 3 malignant tumours, but not in benign tumours or normal cartilage. Analysis of the p53 gene revealed an unchanged structure in all samples. These findings show a role for p16, but not p53, in chondrosarcoma.

Adolescent↗
PubMed2000

Two- to 9-year outcome after autologous chondrocyte transplantation of the knee.

Autologous cultured chondrocyte transplantation was introduced in Sweden in 1987 for the treatment of large (1.5-12.0 cm2) full thickness chondral defects of the knee. The clinical, arthroscopic, and histologic results from the first 101 patients treated using this technique are reported in this study. Patients were assessed retrospectively using three types of endpoints: patient and physician derived clinical rating scales (five validated and two new); arthroscopic assessment of cartilage fill, integration, and surface hardness; and standard histochemical techniques. Ninety-four patients with 2- to 9-years followup were evaluable. Good to excellent clinical results were seen in individual groups as follows: isolated femoral condyle (92%), multiple lesions (67%), osteochondritis dissecans (89%), patella (65%), and femoral condyle with anterior cruciate ligament repair (75%). Arthroscopic findings in 53 evaluated patients showed good repair tissue fill, good adherence to underlying bone, seamless integration with adjacent cartilage, and hardness close to that of the adjacent tissue. Hypertrophic response of the periosteum or graft or both was identified in 26 arthroscopies; seven were symptomatic and resolved after arthroscopic trimming. Graft failure occurred in seven (four of the first 23 and three of the next 78) patients. Histologic analysis of 37 biopsy specimens showed a correlation between hyalinelike tissue (hyaline matrix staining positive for Type II collagen and lacking a fibrous component) and good to excellent clinical results. The good clinical outcomes of autologous chondrocyte transplantation in this study are encouraging, and clinical trials are being done to assess the outcomes versus traditional fibrocartilage repair techniques.

Activities of Daily Living↗
PubMed2000

Insulin sensitivity and hemostatic factors in clinically healthy 58-year-old men.

The objective of this cross-sectional study was to investigate the relationship between factors of the coagulation- and fibrinolysis systems and insulin sensitivity in 104 clinically healthy, 58-years-old men. Insulin sensitivity (hyperinsulinemic euglycemic clamp) adjusted for lean body mass, the metabolic syndrome according to a suggested definition, and different factors in the coagulation- and fibrinolysis system were determined. Subjects with the metabolic syndrome were characterised by increases in PAI-1 activity, tPA antigen, protein C and protein S and low concentrations of tPA activity. Insulin sensitivity was independently and reversibly associated with PAI-1 (p = 0.014) and directly with tPA activity (p = 0.001). Insulin sensitivity was also significantly negatively associated with protein S and protein C and several components in the metabolic syndrome, however not remaining significant in multivariate analyses. Protein C and protein S were significantly associated with PAI-1 activity, tPA activity (negatively), tPA antigen and antithrombin III. In conclusion, the data indicated that insulin resistance and several of the clustering components in the metabolic syndrome are accompanied by increased plasma concentrations of the anticoagulatory proteins C and S which may represent a mechanism which counteracts the concomitantly occurring hypofibrinolysis.

Blood Coagulation↗
PubMed2000

No evidence for the involvement of the multidrug resistance-associated protein and/or the monocarboxylic acid transporter in the intestinal transport of fluvastatin in the rat.

Fluvastatin, an amphiphilic anion, shows a nonlinear increase in effective intestinal permeability (P(eff)) with increasing lumenal concentrations in rats. The main objective of this study was to investigate whether or not this observation could be attributed to an efflux-mediated transport by the multidrug resistance-associated protein (MRP). In parallel, we investigated the possible involvement of the monocarboxylic acid transporter (MCT) in the rapid intestinal absorption of fluvastatin. Single-pass perfusions were performed in the ileum and colon of the rat, with and without the presence of well-established inhibitors/substrates for the MRP (probenecid) and the MCT (nicotinic acid). The results suggest that neither the MRP nor the MCT are involved to any significant extent in the absorption process of fluvastatin in the rat intestine. Thus, the previously reported concentration-dependent P(eff) of fluvastatin in these intestinal regions of the rat is probably not attributable to saturation of any efflux mediated by MRP.

Acyl Coenzyme A↗
PubMed1999

Risk factors for low back pain in a cohort of 1389 Danish school children: an epidemiologic study.

This study was designed as a cross-sectional questionnaire-based survey of low back pain (LBP) in 13- to 16-year-old Danish school children. The cohort consisted of 671 boys and 718 girls in eighth and ninth grade in 46 municipal schools in three counties of Sealand. All the pupils filled in a questionnaire with LBP as the main topic and were at the same time examined by the school doctors. The first part of the questionnaire contained questions about leisure time sports activity, TV watching, PC use, job in leisure time and smoking. The second part dealt with LBP in relation to frequency and severity, influence on daily living and use of the health system. The school doctor measured body height and weight, (BMI), degree of hypermobility and the tightness of the hamstring muscles. The results showed a cumulative life-time prevalence of LBP of 58.9%, a 1-year prevalence of 50.8% and an increase in LBP prevalence of 6.4% from 14 to 15 years of age, independent of gender. Fourteen percent (141 F, 54 M) fulfilled the criteria for general hypermobility and 12.2% (45 F, 124 M) had tightness of hamstring muscles of more than 40 degrees. Recurrent/continuous LBP in a moderate to severe degree was recorded in 19.4% of children (182 F, 88 M). This was positively correlated to female gender, BMI more than 25 kg/m(2), competitive sport for boys, poor physical fitness, daily smoking, heavy jobs in leisure time, increased use of the health system and reduced life quality. Stepwise logistic regression analysis indicates that female gender, daily smoking and heavy jobs are important associated factors for severe LBP in adolescents, with an observed probability of 46% if all factors are present. We don't know yet whether these factors are of any causal importance in the development of severe LBP.

Adolescent↗