Search PubMed⌕ Search

Biomedical subjects

T S Sørensen

Publications and source records attributed to T S Sørensen.

At least 19 recordsLinked to original sources
PubMed2001

A new virtual reality approach for planning of cardiac interventions.

A novel approach to three-dimensional (3D) visualization of high quality, respiratory compensated cardiac magnetic resonance (MR) data is presented with the purpose of assisting the cardiovascular surgeon and the invasive cardiologist in the pre-operative planning. Developments included: (1) optimization of 3D, MR scan protocols; (2) dedicated segmentation software; (3) optimization of model generation algorithms; (4) interactive, virtual reality visualization. The approach is based on a tool for interactive, real-time visualization of 3D cardiac MR datasets in the form of 3D heart models displayed on virtual reality equipment. This allows the cardiac surgeon and the cardiologist to examine the model as if they were actually holding it in their hands. To secure relevant examination of all details related to cardiac morphology, the model can be re-scaled and the viewpoint can be set to any point inside the heart. Finally, the original, raw MR images can be examined on line as textures in cut-planes through the heart models.

Cardiovascular Diseases↗
PubMed2000

Functional rest through intensive treatment with insulin and potassium channel openers preserves residual beta-cell function and mass in acutely diabetic BB rats.

Diazoxide and the diazoxide-analogue, NNC 55-0118, are potassium channel openers that interfere with insulin secretion from beta-cells. In vitro, we show that these two drugs inhibit insulin release from diabetes-resistant BB rat islets cultured at either low or high glucose concentration and cause an intracellular accumulation of insulin with high glucose. Preservation of beta-cells was investigated in newly diabetic BB rats treated with insulin implants from day 0-8 under oral diazoxide, NNC 55-0118 or solvent gavage once a day from day 0-7. Three of eight rats (37.5%) treated with diazoxide and three of ten (30%) treated with NNC 55-0118 retained near normal C-peptide responses when challenged with glucose/arginine on day 9, whereas none of eight (0%) solvent-treated rats showed a C-peptide response. Immunohistochemical staining for insulin and glucagon showed that all the C-peptide responding rats had insulin-positive cells in their islets. In contrast, islets from non-responding rats displayed marked inflammation or end-stage lesions. Furthermore, rats with C-peptide response and treated with NNC 55-0118 exhibited only minimal signs of islet inflammation, whereas C-peptide responding diazoxide-treated rats had low level islet inflammation. These results imply that it is conceivable to preserve residual beta-cells at diabetes onset by induction of target cell rest with potassium channel openers and continuous insulin treatment.

Animals↗
PubMed1998

Functional interplay between p53 and E2F through co-activator p300.

Both E2F and p53 are sequence specific transcription factors that regulate early cell cycle progression. The pathway of control mediated through E2F governs the transition from G1 into S phase whereas p53 in response to genotoxic stress can facilitate cell cycle arrest or apoptosis. The mechanisms which influence the outcome of p53 induction are not clear, although transcription of the p53 target gene, encoding the cdk-inhibitor p21(Waf1/Cip1), correlates with p53-mediated cell cycle arrest. Here using a combination of biochemical and functional assays we identify p300 as a co-activator required for p53-dependent transcriptional activation of Waf1/Cip1. Furthermore, we show that the cdk-inhibitor p21(Waf1/Cip1) autoregulates in a positive fashion transcription through modulating the activity of the p53/p300 complex, whilst negatively regulating the activity of E2F by preventing cdk-dependent phosphorylation of pRb. Consistent with a role for p21(Waf1/Cip1) in the autoregulation of p53-dependent transcription, p300 augments the ability of p53 to cause G1 arrest and, conversely, cells undergoing p53-dependent apoptosis are rescued by p300. Thus, our data suggest that the ability of p300 to interact with p53 influences the physiological consequence of p53 activation. From previous studies it is known that cells expressing aberrant levels of E2F-1 can undergo p53-dependent apoptosis. In addition, we find that E2F-1 can cause apoptosis in p53-/- tumour cells and further p300, which also functions as a co-activator for the E2F/DP heterodimer, enhances the apoptotic activity of E2F-1. In conditions where E2F-1 and p53 co-operate in apoptosis E2F-1 can effectively compete for p300, causing a reduction in p53-dependent transcription. Thus, a functional interaction between p300 and either p53 or E2F-1 has a profound impact on early cell cycle progression, specifically in regulating the contrasting outcomes of cell cycle arrest and apoptosis. These results suggest a critical role for p300 in integrating and co-ordinating the functional interplay between the pathways of growth control mediated by E2F and p53.

Binding Sites↗
PubMed1998

Ankle arthroplasty for rheumatoid arthritis and osteoarthritis: prospective long-term study of cemented replacements.

We performed 52 cemented ankle arthroplasties for painful osteoarthritis (OA) (25) or rheumatoid arthritis (RA) (27) using an ankle prosthesis with a near-anatomical design. We assessed the patients radiologically and clinically for up to 14 years using an ankle scoring system. The preoperative median scores were 29 for the OA group and 25 for the RA group and at ten years were 93.5 and 83, respectively. Six ankles in the OA group and five in the RA group required revision or arthrodesis. Survivorship analysis of the two groups showed no significant differences with 72.7% survival for the OA group and 75.5% for the RA group at 14 years.

Adult↗
PubMed1997

The predominant E2F complex in human primary haemopoietic cells and in AML blasts contains E2F-4, DP-1 and p130.

The E2F family of transcription factors are thought to play an important role in the control of cell cycle progression. There is now also increasing evidence that some family members may act as oncogenes or tumour suppressor genes. The characterization of these proteins in human primary haemopoietic cells and acute myeloid leukaemia (AML) blasts may thus give an insight to the molecular mechanisms governing proliferation and leukaemogenesis in these cells. Therefore we analysed the expression of E2F-DNA binding activity and the constituent proteins found in the complexes in human primary haemopoietic cells of various lineages. We also studied blasts from 18 patients with acute myeloid leukaemia (AML). On electromobility shift assays (EMSA) a single E2F-DNA binding complex was detected in T cells, B cells and monocytes which was shown to contain E2F-4, DP-1 and p130, indicating that all quiescent haemopoietic cells have the same complex. Examination of 18 AML samples by EMSA revealed the presence of E2F binding and no gross abnormalities were detected. An E2F-4/p130 complex was detected in representative samples of all FAB types analysed. Thus abnormalities of E2F function are unlikely to play a primary pathogenic role in AML.

Blotting, Western↗
PubMed1997

Orthopedic wound infections. 182 cases after 8913 operations during an 8-year survey.

We performed a surveillance of postoperative wound infections at our department for a period of 8 years. The surveillance was based on forms completed by the surgeons at the department. Retrospectively, by scrutinizing the records of patients with recorded infections, the criteria for infections used by the surgeons were compared with the criteria recommended by the Centers for Disease Control, USA, for routine infection surveillance studies: 1) pus present in the wound, 2) bacteria isolated from the wound, 3) spontaneous wound breakdown or surgical intervention due to suspected infection; if culture is performed, it must be positive, 4) evidence of infection at reoperation or at radiologic or histopathologic examination (restricted to deep infections) or 5) diagnosis of infection by a surgeon. 182 infections were recorded; in 106 (58%) pus was present, drained either spontaneously or by surgical intervention, in 24 (13%) no pus was seen, but the culture was positive. In 116 cases, surgical intervention was performed or wounds spontaneously broke down; pus was found in 101 of these and culture of non-purulent material was positive in 13 and negative in 2. In 52 (29%) patients, only criterion 5 was fulfilled. In surveillance studies where the recordings are based on several observers, the subjective criterion 5 may, as in our study, give a falsely high number of infections, also preventing comparison between studies. We recommend that all suspected infections are cultured and that only criteria 1, 2 and 4 are used.

Humans↗
PubMed1996

Oxygen transport through methacrylate-based hydrogels with potential biological capability.

The permeability to oxygen of hydrogels prepared from copolymers of 2-hydroxymethyl methacrylate and p-methacryloxyl-oxyacetanilide have been studied by using an oxygen electrode in combination with a permeometer. The transmissibility Dk/L and the permeability Dk (where D, k and L are, respectively, the diffusion coefficient, the Henry constant and the thickness of the hydrogel) are measured by a combination of steady state and transitory state measurements. Both transport coefficients increase with the water content, which in turn depends on the copolymer composition. The values of these quantities tend toward a limiting value for water-saturated hydrogels. The ratio of the characteristic volume for diffusion of the oxygen molecule to the free volume of water per mole water is found to be in the vicinity of 0.10, and this value increases slightly as the fraction of the hydrophilic comonomer in the hydrogel increases. A detailed comparison of the biogels studied with six commercial contact lenses has also been performed.

Acetanilides↗
PubMed1996

Functional interaction between DP-1 and p53.

The cellular transcription factor DRTF1/E2F and the tumor suppressor protein p53 play important roles in controlling early cell cycle events. DRTF1/E2F is believed to coordinate and integrate the transcription of cell cycle-regulating genes, for example, those involved in DNA synthesis, with the activity of regulatory proteins, such as the retinoblastoma tumor suppressor gene product (pRb), which modulate its transcriptional activity. In contrast, p53 is thought to monitor the integrity of chromosomal DNA and when appropriate interfere with cell cycle progression, for example, in response to DNA damage. Generic DRTF1/E2F DNA binding activity and transcriptional activation arise when members of two distinct families of proteins, such as DP-1 and E2F-1, interact as DP/E2F heterodimers. In many cell types, DP-1 is a widespread component of DRTF1/E2F DNA binding activity which when expressed at high levels oncogenically transforms embryonic fibroblasts. Here, we document an association between DP-1 and p53 and demonstrate its presence in mammalian cell extracts. In vitro p53 interacts with an immunochemically distinct form of DP-1 and in vivo can regulate transcription driven by the DP-1/E2F-1 heterodimer. At the biochemical level, p53 competes with E2F-1 for DP-1, with a consequent reduction in DNA binding activity. Mutational analysis defines within DP-1 a C-terminal region required for the interaction with p53 and within p53 an N-terminal region distinct from that required to bind to MDM2. Our results establish DRTF1/E2F as a common cellular target in growth control mediated through the activities of pRb and p53 and suggest an alternative mechanism through which p53 may regulate cellular proliferation.

Animals↗
PubMed1995

Stimulation of E2F1/DP1 transcriptional activity by MDM2 oncoprotein.

The MDM2 proto-oncogene is found amplified in a variety of tumours. The oncogenic capacity of the MDM2 protein is attributed to its ability to bind the p53 tumour-suppressor protein and mask its transcriptional activation potential. Here we show that MDM2 makes a functional contact with two cooperating transcription factors, E2F1 and DP1 (refs 4,5), which are involved in S-phase progression. MDM2 contacts the activation domain of E2F1 using residues conserved in the activation domain of p53. However, in contrast to its repression of p53 activity, MDM2 stimulates the activation capacity of E2F1/DP1. These results indicate that MDM2 not only releases a proliferative block by silencing the tumour suppressor p53, it also positively augments proliferation by stimulating the S-phase inducing transcription factors E2F1/DP1.

3T3 Cells↗
PubMed1994

DP-1: a cell cycle-regulated and phosphorylated component of transcription factor DRTF1/E2F which is functionally important for recognition by pRb and the adenovirus E4 orf 6/7 protein.

The cellular transcription factor DRTF1/E2F integrates cell cycle events with the transcription apparatus through its cyclical interactions with important regulators of cellular proliferation. Two sequence-specific DNA binding proteins, DP-1 and E2F-1, are components of DRTF1/E2F which synergistically interact in a DP-1/E2F-1 heterodimer. Here, we show that DP-1 is a very frequent, possibly universal, component of DRTF1/E2F in 3T3 cells since it is present in all forms of the DNA binding activity that occur during cell cycle progression. Furthermore, the DP-1 polypeptide, which is phosphorylated, undergoes a phosphorylation-dependent mobility shift during the cell cycle suggesting that its level of phosphorylation is regulated during cell cycle progression. A C-terminal region in DP-1 can interact with pRb which, in the context of the DP-1/E2F-1 heterodimer, contributes to the efficiency of pRb binding. The DP-1/E2F-1 heterodimer specifically interacts with the adenovirus type 5 E4 orf 6/7 protein, to produce a DNA binding activity which binds co-operatively to, and transcriptionally activates through, two appropriately positioned E2F sites in a manner which resembles the regulation of DRTF1/E2F by E4 orf 6/7 during adenovirus infection. We conclude that DP-1 is a frequent and cell cycle-regulated component of DRTF1/E2F, and that in the DP-1/E2F-1 heterodimer it is functionally important for recognition by pRb and the E4 orf 6/7 protein.

3T3 Cells↗
PubMed1993

[Finger tip injuries. A comparative study of silver sulfadiazine and fucidin gauze].

Eighty-eight superficial finger-tip lesions were randomized after thorough cleaning to either silver sulphadiazine treatment of Fucidin fusidic acid gauze. In the silver sulphadiazine group the wounds were covered with a non-sterile PVC gloce and redressed at least every third day; in the other group Fucidin gauze was applied and a tubigauze dressing was left in situ for ten days, after which a new dressing was applied. All patients were treated until healed and followed for at least six months after injury. Patients in the silver sulphadiazine group required shorter time for healing and shorter sick leave. The treatment is recommended because of the easy procedure and the good results.

Adult↗
PubMed1993

Bactericidal activity of gentamicin against S. aureus. In vitro study questions value of prolonged high concentrations.

Bactericidal activity of gentamicin against 4 strains of Staphylococcus aureus was investigated in vitro using Mueller-Hinton broth (MH) and surgical wound fluid (WF) as test media. 6 concentrations of gentamicin were tested ranging from 1-1024 micrograms/mL. During the first hour of incubation, there was a marked concentration-dependent kill rate, approximately 3 x 10(3) times in WF and 10(2) times in MH. After the first hour of incubation, the kill rate was independent of the concentration in both media. Our study questions the benefit of the prolonged and high wound concentrations of gentamicin obtained after application of gentamicin-containing PMMA.

Gentamicins↗
PubMed1991

The effect of intra-articular instillation of bupivacaine on postarthroscopic morbidity: a placebo-controlled, double-blind trial.

Forty patients undergoing diagnostic arthroscopy of the knee were included in a randomized double-blind study to investigate the effect of bupivacaine on postarthroscopic morbidity. The arthroscopies were performed under local anesthesia using 1% lidocaine with adrenaline. At the conclusion of the arthroscopic examination, 10 ml 0.5% bupivacaine with adrenaline or 10 ml placebo was instilled and left in the joint cavity. The two groups of patients were compared with regard to postarthroscopic duration of the anesthesia, degree of postarthroscopic pain, number of analgesic tablets taken, need for crutches or other walking aids, and days away from work. There was no difference between the patients receiving bupivacaine and patients receiving placebo for any of the parameters investigated.

Adult↗
PubMed1991

Clinical and pharmacokinetic evaluation of gentamycin containing collagen in groin wound infections after vascular reconstruction.

Fourteen patients with localised groin wound graft infection after vascular reconstruction were included in this study to evaluate the clinical effect and the pharmacokinetic profile of gentamycin containing collagen for local antibiotic treatment. All patients were treated by surgical revision and the implantation of one collagen sponge containing 130 mg gentamycin in addition to systemic antibiotics. At follow-up (median 10 months, range 6-15 months), 13 of the 14 patients were cured with a patent reconstruction, giving a success rate in this series of 93%. The pharmacokinetic study showed a very high initial gentamycin concentration in wound fluid, which neatly exceeded the MIC values for most bacteria normally considered resistant to gentamycin. These high MIC values were sustained for 2 to 3 days. In conclusion, this study demonstrated a good clinical effect of gentamycin containing collagen with a high cure rate. In the wound fluid an initial high concentration of gentamycin was achieved which lasted for 2-3 days.

Aged↗
PubMed1991

Bacterial growth on suction drain tips. Prospective study of 489 clean orthopedic operations.

The study included 489 clean orthopedic operations with implantation of major foreign materials (joint replacements and internal fixations of fractures). Specimens for culture were taken from the suction drainage system, either from the drain fluid or from the drain-tube tip or from both. Six superficial and five deep infections were seen following the operations. Only two cultures of drain fluid were positive, and neither of these became infected. Positive drain-tip cultures were seen after 56 operations, and of these, five were followed by infection. The risk of infection was increased if Staphylococcus aureus, Enterobacteriaceae, or Streptococcus faecalis was cultured from drain tips. Drain-tip cultures growing only coagulase-negative staphylococci, nonhemolytic streptococci, and corynebacteria were not correlated with increased risk of infection. There was a not significant tendency towards fewer infections if positive drain-tip cultures with virulent bacteria were treated with specific antibiotics.

Bacteria↗
PubMed1990

Rapid release of gentamicin from collagen sponge. In vitro comparison with plastic beads.

The gentamicin-containing collagen sponge is a new product intended for local application in bone and soft-tissue infections. The release of gentamicin from the collagen sponges was compared in vitro to that from polymethyl-methacrylate (PMMA) beads. A static and kinetic experimental design was used. In the static model, pieces of collagen sponge or PMMA beads were added to 20 mL of distilled water, and during the following hours the gentamicin concentrations in the water were repeatedly measured. This simple model was extended to the kinetic model as the released gentamicin was removed from the water exponentially by means of an infusion-withdrawal pump. The gentamicin was released from the carrier substances with increasing half lives. During the first 4 hours, the half life increased from 0.2 to 1.5 hours for the collagen sponge and from 3 to 78 hours for the PMMA beads. After 1.5 hours, 95 percent of the gentamicin was released from the sponges, whereas only 8 percent was released from the beads.

Collagen↗
PubMed1989

Elimination of cefuroxime and gentamicin during and after open heart surgery.

In eight consecutive adult heart surgery patients, serum concentrations of cefuroxime and gentamicin were studied during and after operation. Repeated doses of cefuroxime 1.5 g and gentamicin 80 mg were given. Intra-operative concentrations were deemed adequate (cefuroxime Cmin: 16-45 mg/l, gentamicin Cmin: 1.6-2.8 mg/l), and no differences (P = 0.05) could be demonstrated between elimination rates during and after open heart operation (cefuroxime T1/2 101 vs 111 min, gentamicin T1/2 191 vs 193 min).

Adult↗