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Biomedical subjects

T Lund

Publications and source records attributed to T Lund.

At least 37 records · Page 2Linked to original sources
PubMed2001

Refocusing of B-cell responses following a single amino acid substitution in an antigen.

Intranasal immunization of BALB/c strain mice was carried out using baculovirus-derived human chorionic gonadotrophin (hCG) beta-chain, together with Escherichia coli heat-labile enterotoxin. Gonadotrophin-reactive immunoglobulin A (IgA) was induced in a remote mucosal site, the lung, in addition to a systemic IgG response. The extensive sequence homology with luteinizing hormone (LH) results in the production of LH cross-reactive antibodies when holo-hCG is used as an immunogen. In contrast to wild-type hCGbeta, a mutated hCGbeta-chain containing an arginine to glutamic acid substitution at position 68 did not induce the production of antibodies which cross-react with LH. Furthermore, the epitopes utilized in the B-cell response to the mutated hCGbeta shifted away from the immunodominant region of the parent wild-type molecule towards epitopes within the normally weakly immunogenic C terminus. This shift in epitope usage was also seen following intramuscular immunization of rabbits. Thus, a single amino acid change, which does not disrupt the overall structure of the molecule, refocuses the immune response away from a disadvantageous cross-reactive epitope region and towards a normally weakly immunogenic but antigen-unique area. Similar mutational strategies for epitope-refocusing may be applicable to other vaccine candidate molecules.

Administration, Intranasal↗
PubMed2001

Fibrinogen increases lipopolysaccharide-induced tumor necrosis factor-alpha and interleukin-8 release, and enhances tissue factor activity in monocytes in a modified whole blood system.

The objective of this study was to investigate the effect of fibrinogen on lipopolysaccharide (LPS)-stimulated blood cells. To this end, a minimum essential blood system was established, reconstituted from washed blood cells and 20% (fibrinogen-free) lepirudin anticoagulated serum in RPMI-1640. Concurrent addition to the system of 1.0-4.0 mg/ml fibrinogen increased LPS-induced tissue factor (TF) activity in the monocytes in a dose-dependent manner. This enhancing effect was, by and large, independent of the LPS concentration (0.5-5.0 ng/ml). Even at the lowest concentration of fibrinogen (1.0 mg/ml), the enhancing effect was quite significant (46-80%) at almost every concentration of LPS tested. Furthermore, LPS-induced release of the two proinflammatory products tumor necrosis factor-alpha and interleukin-8 were also enhanced by added fibrinogen. In conclusion, fibrinogen is capable of enhancing the emergence of certain proinflammatory molecules as well as the procoagulant factor TF, effects that may very well in part be accountable for fibrinogen-related risk of ischemic heart disease and stroke.

Dose-Response Relationship, Drug↗
PubMed2001

Relationship between interstitial fluid volume and pressure (compliance) in hypothyroid rats.

There is clinical and experimental evidence that lack of thyroid hormones may affect the composition and structure of the interstitium. This can influence the relationship between volume and pressure during changes in hydration. Hypothyrosis was induced in rats by thyroidectomy 8 wk before the experiments. Overhydration was induced by infusion of acetated Ringer, 5, 10, and 20% of the body weight, while fluid was withdrawn by peritoneal dialysis with hypertonic glucose. Interstitial fluid pressure (P(i)) in euvolemia (euvolemic control situation) and experimental situation was measured with micropipettes connected to a servocontrolled counterpressure system. The corresponding interstitial fluid volume (V(i)) was found as the difference between extracellular fluid volume measured as the distribution volume of (51)Cr-labeled EDTA and plasma volume measured using (125)I-labeled human serum albumin. In euvolemia, V(i) was similar or lower in the skin and higher in skeletal muscle of hypothyroid than in euthyroid control rats, whereas the corresponding P(i) was higher in all tissues. During overhydration, P(i) rose to the same absolute level in both types of rats, whereas during peritoneal dialysis there was a linear relationship between volume and pressure in all tissues and types of rats. Interstitial compliance (C(i)), calculated as the inverse value of the slope of the curve relating changes in volume and pressure in dehydration, did not differ significantly in the hindlimb skin of hypothyroid and euthyroid rats. However, in skeletal muscle, C(i) was 1.3 and 2.0 ml. 100 g(-1). mmHg(-1) in hypothyroid and euthyroid rats (P < 0.01), with corresponding numbers for the back skin of 2.7 and 5.0 ml. 100 g(-1). mmHg(-1) (P < 0.01). These experiments suggest that lack of thyroid hormones in rats changes the interstitial matrix, again leading to reduced C(i) and reduced ability to mobilize fluid from the interstitium.

Animals↗
PubMed2000

A low budget luminometer for sensitive chemiluminescent immunoassays.

We have designed a simple luminometer based on a reasonably priced Peltier-cooled charge-coupled device (CCD) camera, housed in a light-tight box, with straightforward lens imaging and a simple platform for a microtitre or other assay format. The quantitative readout of the CCD image is recorded on a PC using customised software. The instrument can be assembled in a standard university workshop for under pound3000, compared with the cheapest commercial instruments retailing at pound10,000 and above. Consistent with the general view on chemiluminescent assays, the sensitivity is 10-100 times greater than that obtained with parallel ELISA's using a chromogenic substrate. A unique feature of the CCD format is that it enables assays to be carried out on arrays of minidots and even nanodots of antigen on the floor of each microtitre well. This permits direct comparison and standardisation of reactivity of a single sample against several antigens and economy in the use of reagents, test sample and technician time; finger-prick samples of blood can be analysed. The instrument should have widespread applicability in developing countries and, indeed, in any laboratories with hard-pressed budgets.

Animals↗
PubMed2000

Computer-assisted spine surgery.

Computer assistance has been shown to improve significantly the accuracy and safety of pedicle screw insertion under clinical conditions. The technique of image-guided navigation is described in this article, based on the authors' clinical experience of over 4 years. The value of navigation systems for preoperative planning is discussed. Clinical results of the application of this new method in the cervical, thoracic, and lumbosacral spine as well as the iliosacral joints are presented by means of the authors' own studies and reports from the literature. Pros and cons of computer guidance are discussed. The authors predict computer navigation will be used in percutaneous and minimally invasive procedures in the near future.

Clinical Trials as Topic↗
PubMed2000

A new approach to computer-aided spine surgery: fluoroscopy-based surgical navigation.

A new computer-based navigation system for spinal surgery has been designed. This was achieved by combining intraoperative fluoroscopy-based imaging using conventional C-arm technology with free-hand surgical navigation principles. Modules were developed to automate digital X-ray image registration. This is in contrast to existing computed tomography- (CT) based spinal navigation systems, which require a vertebra-based registration procedure. Cross-referencing of the image intensifier with the surgical object allows the real-time image-interactive navigation of surgical tools based on one single registered X-ray image, with no further image updates. Furthermore, the system allows the acquisition and real-time use of multiple registered images, which provides an advanced multi-directional control (pseudo 3D) during surgical action. Stereotactic instruments and graphical user interfaces for image-interactive transpedicular screw insertion have been developed. A detailed validation of the system was performed in the laboratory setting and throughout an early clinical trial including eight patients in two spine centers. Based on the resulting data, the new technique promises improved accuracy and safety in open and percutaneous spinal surgery.

Bone Screws↗
PubMed2000

Biomechanics of stand-alone cages and cages in combination with posterior fixation: a literature review.

Interbody cages in the lumbar spine have met with mixed success in clinical studies. This has led many investigators to supplement cages with posterior instrumentation. The objective of this literature review is to address the mechanics of interbody cage fixation in the lumbar spine with respect to three-dimensional stabilization and the strength of the cage-vertebra interface. The effect of supplementary posterior fixation is reviewed. Only three-dimensional stabilization evaluations in human cadaveric models are included. These studies involve the application of different loads to the spine and the measurement of vertebral motion in flexion-extension, axial rotation, and lateral bending. There are no published studies which detected any differences between different cage designs. However, it does seem that cages inserted from an anterior direction provide better stabilization to the spine than those inserted from a posterior direction. In general, anterior cages stabilize better than posterior cages in axial rotation and lateral bending. Cages from both directions stabilized well in flexion, but not in extension. Supplementary posterior fixation with pedicle or translaminar screws substantially improves the stabilization in all directions. The strength of the cage-vertebra interface from studies using human cadaveric specimens is also reviewed. The axial compressive strength of this interface is highly dependent upon vertebral body bone density. Other factors such as preservation of the subchondral bony end-plate and cage design are clearly less important in the compressive strength. Supplementary posterior instrumentation does not enhance substantially the interface strength in axial compression.

Biomechanical Phenomena↗
PubMed2000

[Computer-assisted spine surgery: principles, technique, results and perspectives].

Computer-assisted techniques were introduced in spine surgery in the 1990s to improve accuracy and safety of operative procedures. Several reports on clinical results of computer-aided screw insertion in the cervical, thoracic, and lumbar spine as well as the sacro-iliac joints are available. They show a significant decrease of screw malplacement rates as compared to conventional insertion techniques. The quality of preoperative planning of spinal procedures has improved markedly by using computer navigation systems. Drawbacks, reliability problems, and safety issues of computer navigation are discussed. In the near future, the use of computer guidance for minimally invasive and percutaneous spine procedures is expected.

Bone Screws↗
PubMed2000

Accuracy of pedicle screw insertion with and without computer assistance: a randomised controlled clinical study in 100 consecutive patients.

We performed a randomised controlled study to assess the accuracy of computer-assisted pedicle screw insertion versus conventional screw placement under clinical conditions. One hundred patients scheduled for posterior thoracolumbar or lumbosacral pedicle screw instrumentation were randomised into two groups, either for conventional pedicle screw placement or computer-assisted screw application using an optoelectronic navigation system. From the computer-assisted group, nine patients were excluded: one because of an inadequate preoperative computed tomography study, seven because of problems with the specific instruments or the computer system, and one because of an intraoperative anesthesiological complication. Thus, there were 50 patients in the conventional group and 41 in the computer-assisted group, and the number of screws inserted was 277 and 219, respectively. There was no statistical difference between the groups concerning age, gender, diagnosis, type of operation performed, mean operating time, blood loss, or number of screws inserted. The time taken for screw insertion was significantly longer in the computer-assisted group. Postoperatively, screw positions were assessed by an independent radiologist using a sophisticated CT imaging protocol. The pedicle perforation rate was 13.4% in the conventional group and 4.6% in the computer-assisted group (P = 0.006). Pedicle perforations of more than 4 mm were found in 1.4% (4/277) of the screw insertions in the conventional group, and none in the computer-assisted group. Complications not related to pedicle screws were two L5 nerve root lesions, one end plate fracture, one major intraoperative bleeding and one postoperative death in the conventional group, and one deep infection in the computer-assisted group. In conclusion, pedicular screws were inserted more accurately with image-guided computer navigation than with conventional methods.

Adult↗
PubMed2000

Minimizing stochastic complexity using local search and GLA with applications to classification of bacteria.

In this paper, we compare the performance of two iterative clustering methods when applied to an extensive data set describing strains of the bacterial family Enterobacteriaceae. In both methods, the classification (i.e. the number of classes and the partitioning) is determined by minimizing stochastic complexity. The first method performs the minimization by repeated application of the generalized Lloyd algorithm (GLA). The second method uses an optimization technique known as local search (LS). The method modifies the current solution by making global changes to the class structure and it, then, performs local fine-tuning to find a local optimum. It is observed that if we fix the number of classes, the LS finds a classification with a lower stochastic complexity value than GLA. In addition, the variance of the solutions is much smaller for the LS due to its more systematic method of searching. Overall, the two algorithms produce similar classifications but they merge certain natural classes with microbiological relevance in different ways.

Algorithms↗
PubMed2000

Dynamic evaluation of fluid shifts during normothermic and hypothermic cardiopulmonary bypass in piglets.

BACKGROUND: Edema, generalized overhydration and organ dysfunction commonly occur in patients undergoing open-heart surgery using cardiopulmonary bypass (CPB) and induced hypothermia. Activation of inflammatory reactions induced by contact between blood and foreign surfaces are commonly held responsible for the disturbances of fluid balance ("capillary leak syndrome"). We used an online technique to determine fluid shifts between the intravascular and the interstitial space during normothermic and hypothermic CPB. METHODS: Piglets were placed on CPB (fixed pump flow) via thoracotomy in general anesthesia. In the normothermic group (n=7), the core temperature was kept at 38 degrees C prior to and during 2 h on CPB, whereas in the hypothermic group (n=7) temperature was lowered to 28 degrees C during bypass. The CPB circuit was primed with acetated Ringer's solution. The blood level in the CPB circuit reservoir was held constant during bypass. Ringer's solution was added when fluid substitution was needed (falling blood level in the reservoir). In addition to invasive hemodynamic monitoring, fluid input and losses were accurately recorded. Inflammatory mediators or markers were not measured in this study. RESULTS: Cardiac output, s-electrolytes and arterial blood gases were similar in the two groups in the pre-bypass period. At start of CPB the blood level in the machine reservoir fell markedly in both groups, necessitating fluid supplementation and leading to a markedly reduced hematocrit. This extra fluid need was transient in the normothermic group, but persisted in the hypothermic animals. After 2 h of CPB the hypothermic animals had received 7 times more fluid as compared to the normothermic pigs. CONCLUSION: We found strong indications for a greater fluid extravasation during hypothermic CPB compared with normothermic CPB. The experimental model using the CPB-circuit reservoir as a fluid gauge gives us the opportunity to study further fluid volume shifts, its causes and potential ways to optimize fluid therapy protocols.

Animals↗
PubMed2000

A model of fluid and solute exchange in the human: validation and implications.

In order to understand better the complex, dynamic behaviour of the redistribution and exchange of fluid and solutes administered to normal individuals or to those with acute hypovolemia, mathematical models are used in addition to direct experimental investigation. Initial validation of a model developed by our group involved data from animal experiments (Gyenge, C.C., Bowen, B.D., Reed, R.K. & Bert, J.L. 1999b. Am J Physiol 277 (Heart Circ Physiol 46), H1228-H1240). For a first validation involving humans, we compare the results of simulations with a wide range of different types of data from two experimental studies. These studies involved administration of normal saline or hypertonic saline with Dextran to both normal and 10% haemorrhaged subjects. We compared simulations with data including the dynamic changes in plasma and interstitial fluid volumes VPL and VIT respectively, plasma and interstitial colloid osmotic pressures PiPL and PiIT respectively, haematocrit (Hct), plasma solute concentrations and transcapillary flow rates. The model predictions were overall in very good agreement with the wide range of experimental results considered. Based on the conditions investigated, the model was also validated for humans. We used the model both to investigate mechanisms associated with the redistribution and transport of fluid and solutes administered following a mild haemorrhage and to speculate on the relationship between the timing and amount of fluid infusions and subsequent blood volume expansion.

Animals↗
PubMed2000

Distribution of interstitial fluid pressure and fluid volumes in hind-limb skin of rats: relation to meridians?

To determine the distribution of interstitial fluid pressure (Pi) and volume (Vi), and to relate the distribution of these parameters to the distribution of potential meridians located by measurement of electrical impedance, we measured Pi, extracellular fluid (Ve) and plasma volumes (Vp) in 14 pre-defined skin areas, 2 x 2 mm, and in concave and convex regions on the hind-limb and groin of rats in control conditions. Pi was measured with sharpened glass capillaries connected to a servo-controlled counter-pressure system, while Ve and Vp were determined as the extravascular distribution spaces of 51Cr-EDTA and 125I-human serum albumin, respectively. Vi was calculated as Ve - Vp, and Vw as the difference between skin wet and dry weight. Grand mean Pi averaged -0.81 mmHg (SD 0.83, n=95). Pi in skin was significantly higher in lateral and medial parts of the medial aspect of hind-limb compared to pressures in the intermediate area (P<0.05). Pressures in the concave groin and the convex knee area were more negative and positive, respectively, than in the flat intermediate central hind-limb area. There was a significantly higher Vi (P<0.05) and Vw (P<0.05) in the lateral side than that in the medial side. Vp was higher medially and laterally than in the intermediate area (P<0.05 for both comparisons), and correlated positively and significantly with Pi (r=0.66, P<0.05). No correlation was found between Pi and electrical impedance. The study suggests that the distribution of Pi, Vi, Vp and Vw is heterogeneous in hind-limb skin at a macroscopic level without obvious relations to potential meridians.

Animals↗
PubMed2000

A new cytotoxin from Bacillus cereus that may cause necrotic enteritis.

A cytotoxin (CytK) has been isolated from a Bacillus cereus strain that caused a severe food poisoning outbreak killing three people. A protein of 34 kDa was highly cytotoxic, and the addition of other secreted proteins gave no synergistic effect. CytK was also necrotic and haemolytic. No known B. cereus enterotoxins were produced by this strain. A DNA sequence from 1.8 kb upstream to 0.2 kb downstream of the toxin gene was sequenced. The deduced amino acid sequence of the toxin showed similarity to Staphylococcus aureus leucocidins, gamma-haemolysin and alpha-haemolysin, Clostridium perfringens beta-toxin and B. cereus haemolysin II, all belonging to a family of beta-barrel channel-forming toxins. There was no sequence similarity between CytK and enterotoxins of B. cereus. The upstream sequence contained a partial sequence of a putative histidine kinase gene. A recognition site for PlcR, which regulates the transcription of enterotoxins HBL and Nhe of B. cereus, was found in the promoter region of the toxin. This new cytotoxin may be responsible for a disease that is similar to, although not as severe as, the necrotic enteritis caused by the beta-toxin of C. perfringens type C.

Amino Acid Sequence↗
PubMed2000

Is lack of peripheral tolerance induction a cause for diabetes in the non-obese diabetic mouse?

The non-obese diabetic (NOD) mouse is a spontaneous animal model for type 1 diabetes characterized by a selective destruction of the insulin producing beta cells in the pancreas. As in humans, the disease is controlled by several susceptibility genes, some of which map to the major histocompatibility complex on chromosome 17. However, environmental factors also contribute to the development of the disease in the NOD mouse, presumably through controlling the balance between the Th1 and Th2 response in the animal. Recent observations have shown that the NOD mouse has abnormalities in the development of bone marrow-derived antigen-presenting cells. These include the most potent activators of naive T cells, the dendritic cells, which exist in at least two different sub-populations; DC1 cells, responsible for activation of Th1 cells, and DC2 cells, which produce Th2 cells. In addition to activating naive T cells, the dendritic cells are also involved in generating central and peripheral tolerance to self molecules. In this process DC2 cells appear to be more important for the development of peripheral tolerance than DC1 cells. Besides abnormalities in the development of bone marrow-derived antigen-presenting cells, the NOD mouse also has a defect in the thymic selection of T cells, leading to a higher concentration of autoreactive T cells. We speculate that the NOD mouse may develop an imbalance in the two subsets of dendritic cells with a skewing towards DC cells, thus having a reduced ability to generate peripheral tolerance to a number of autoantigens.

Animals↗
PubMed1999

The 105-kDa protein component of Bacillus cereus non-haemolytic enterotoxin (Nhe) is a metalloprotease with gelatinolytic and collagenolytic activity.

A sequence of 91 amino acids residues, probably starting from the N-terminal of the mature protein, was determined for the 105-kDa protein of the non-haemolytic enterotoxin of Bacillus cereus. The last part of this sequence was similar to parts of the N-terminal portions of two collagenases of Clostridium histolyticum and Clostridium perfringens. Zymography, with intact collagen fibril and gelatin as substrates, showed that the 105-kDa protein had collagenolytic and gelatinolytic activity. The 105-kDa protein also showed activity against a typical collagenase substrate, azocoll, and was inhibited by EDTA and 1,10-phenanthroline. We conclude that the 105-kDa protein is a collagenase.

Amino Acid Sequence↗
PubMed1999

The sequence of the non-haemolytic enterotoxin operon from Bacillus cereus.

The non-haemolytic enterotoxin from Bacillus cereus has been sequenced. It is composed of three components, non-haemolytic enterotoxin A, B and C of 41.0, 39.8 and 36.5 kDa, respectively. Transcription of the operon seems to be positively regulated by plcR, a gene that also regulates phospholipase C expression. There is substantial similarity between the three proteins of non-haemolytic enterotoxin and between the non-haemolytic enterotoxin and haemolytic enterotoxin proteins.

Amino Acid Sequence↗