Search PubMed⌕ Search

Biomedical subjects

T Lund

Publications and source records attributed to T Lund.

At least 19 recordsLinked to original sources
PubMed1995

Aspartate at position 57 of nonobese diabetic I-Ag7 beta-chain diminishes the spontaneous incidence of insulin-dependent diabetes mellitus.

MHC class II genes have been shown to influence the development of the autoimmune disease insulin-dependent diabetes mellitus (IDDM) in the nonobese diabetic (NOD) mouse. In human IDDM it has been suggested that the presence of an aspartate at position 57 of the DQ beta-chain might be important in determining resistance to development of IDDM. The involvement of MHC class II genes in IDDM was investigated through the introduction of MHC encoding transgenes. We show that introduction of a mutated I-Ag7 Ab gene which encodes an aspartate at position 57 reduces the incidence of IDDM but does not prevent insulitis, sialadenitis, or the development of insulin and nuclear autoantibodies.

Amino Acid Sequence↗
PubMed1995

A model of fluid resuscitation following burn injury: formulation and parameter estimation.

A dynamic compartmental model is developed to describe the redistribution of fluid and albumin between the circulation and the intact and injured interstitia following burn injury in humans. Transcapillary fluid and albumin exchange is described by a coupled Starling mechanism, while the effect of the burn is represented by time-dependent perturbations to all three compartments. The unknown model parameters are determined for two groups of patients, having less than and greater than 25% total body surface area burns, by statistical fitting of model predictions to patient data from two sources. The parameters include the perturbations to the fluid filtration coefficients in uninjured and injured tissue, GkF,Tl and GkF,BT, respectively, the relaxation coefficient, r, which describes the exponential decay of the perturbations, and the exudation factor, EXFAC, which relates the protein concentration in the exudate to that in the injured tissue. Perturbations to other parameters, including the membrane permeability-surface area product and the albumin reflection coefficient in the injured and uninjured tissues, are determined based on interrelationships with GkF,Tl and GkF,BT. The values of GkF,BT, when corrected for tissue destruction and decreased post-injury perfusion, are in reasonable agreement with the limited experimental data available from the literature. The model and its parameters are further validated by comparing the simulated patient responses to the clinical data used in the parameter estimation as well as to data available from two additional sources.

Body Fluid Compartments↗
PubMed1995

Regulation of human growth hormone-binding protein production by human growth hormone in a hepatoma cell line.

The mechanism by which growth hormone-binding protein (GH-BP) is generated in humans remains unclear. To address this question, we analysed human GH-receptor/GH-BP gene expression in a human hepatoma cell line (HuH7). Northern hybridisation showed that HuH7 cells contain a single mRNA species hybridising with a probe for the sequences encoding the extracellular domain of the hGH-receptor/GH-BP. These data were confirmed by solution hybridisation methods. Thereafter, the cells were treated with r-hGH at physiological (12.5, 25, 50 ng/ml) and supra-physiological (150, 500 ng/ml) concentrations over the period of 48 h. At intervals, RNase protection assays were performed to determine GH-receptor/GH-BP mRNA levels, nuclear run-on assays were carried out to determine whether changes in mRNA levels represented changes in transcription rate, and a radio-ligand binding assay was performed to measure levels of GH-BP in the medium. We found that the r-hGH-regulated changes in GH-receptor/GH-BP mRNA levels detected with the probe for sequences encoding the extracellular domain of human GH-receptor/GH-BP were identical to those previously detected using a probe for the sequences encoding the transmembrane/intracellular domain of the human GH-receptor. In addition, we found that r-hGH had a rapid effect on the levels of GH-BP in the culture medium, which differed from its effect on the GH-receptor/GH-BP mRNA levels. Furthermore, lowering of temperature resulted in a decrease of GH-BP released into the medium implying that enzymes may be involved in the releasing mechanism. These data support the idea that GH-receptor and GH-BP are encoded by a single mRNA species in humans. In addition, they suggest that GH-BP levels are not an accurate reflection of GH-receptor/GH-BP mRNA levels, but that GH-BP production is subject to r-hGH-dependent post-transcriptional regulation, perhaps at the level of post-translational cleavage of the full-length GH-receptor protein. The notion that GH-BP measurements might represent GH-receptor status at the functional level must therefore be taken with caution.

Blotting, Northern↗
PubMed1995

A herpesvirus saimiri protein required for interleukin-2 independence is associated with membranes of transformed T cells.

A region of the herpesvirus saimiri genome encoding an mRNA with two open reading frames (ORFs) has been identified to be essential for transformation of T cells. Deletion of either ORF resulted in the loss of transforming ability. ORF-1 has been shown to code for a collagen-like oncoprotein. This study shows for the first time that the bicistronic mRNA can translate a 32-kDa protein from ORF-2. Polyclonal serum to ORF-2 was generated by using a glutathione fusion protein. Using this antiserum, ORF-2 was localized in cell membranes and is expressed on the outer cell membrane. The half-life of this membrane protein was found to be about 5.5 h. Limited sequence similarity was found between ORF-2 and interleukin-11; however, no secretion of ORF-2 protein was detected in supernatants from transformed cells. Further studies are required to investigate the potential interaction with the interleukin-11 receptor.

Animals↗
PubMed1994

Physical mapping of the rat MHC class II genes shows a high level of interspecies conservation.

We report here a pulsed-field gel electrophoresis map of the rat major histocompatibility complex (MHC) class II region. Using probes for the recently discovered Tap-1 and Tap-2 genes and the different MHC class II genes, we found the gene order in the rat MHC (RT1) region to be RT1.H-Tap-1-Tap-2-Bb-Ba-Db-Da. Moreover, the distance between the Tap-1 and the RT1.Da genes is approximately 150 kb. This, together with recent mapping of the RT1 class II region, demonstrates an extensive colinearity in the MHC region of different species.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1994

Pulsed field gel electrophoretic analysis of the rat major histocompatibility complex class III region shows extensive inter-species conservation.

Using pulsed field gel electrophoresis (PFGE), we have examined the rat major histocompatibility complex (MHC) for the presence of a number of new class III region genes recently identified in the human MHC. We find homologous genes to the human G1, G2, G4, G7a, G9, G9a, G10, G13, G15, and G18 genes, but not the G8 gene in the rat genome, and show that these are linked to the rat TNF-alpha and C4/Slp loci. A long-range restriction map has been constructed on the basis of a PFGE analysis which demonstrates extensive co-linearity in the positions of the homologous sequences in the region between the C4/Slp and TNF loci in the rat MHC when compared with that of the human MHC class III region.

Animals↗
PubMed1994

Alpha-Trinositol inhibits edema generation and albumin extravasation in thermally injured skin.

Pharmacologic attempts to reduce edema generation and albumin extravasation into thermally injured skin have until recently been disappointing unless the drugs (usually antiphlogistic or anti-inflammatory drugs) were given before injury. We have studied the effect of alpha-trinositol (PP56, i.e., 1D-myo-inositol-1,2,6-trisphosphate) given after the injury in an experimental full-thickness 10% TBSA scald burn in anesthetized rats. Total tissue water content (TTW) and albumin extravasation (Ealb) were determined in injured and noninjured skin (series I, n = 12). Interstitial fluid hydrostatic pressure (Pif) was measured in injured skin (series II, n = 14). alpha-Trinositol was administered (alpha-trinositol groups) as an i.v. bolus (40 mg/kg) at 5 minutes after injury followed by an i.v. infusion (1.3 mg/kg/min). In both series a placebo group received burn injury and normal saline in equal volumes instead of alpha-trinositol. Compared with placebo, alpha-trinositol reduced TTW and Ealb as well as the increased negatively of Pif in injured tissue significantly. The effect on Ealb was most prominent, with a reduction from 153.9 +/- 35.6 (SEM) microL/g in the NaCl group to 23.1 +/- 6.3 after alpha-trinositol (p < 0.005). Total tissue water was reduced from 2.51 +/- 0.13 to 2.17 +/- 0.06 mL/g (p < 0.05) and Pif (measured between 21 and 40 minutes postinjury) from -24.7 +/- 4.1 to -3.2 +/- 1.1 mm Hg (p < 0.005).(ABSTRACT TRUNCATED AT 250 WORDS)

Albumins↗
PubMed1994

Studies on the thymus of non-obese diabetic (NOD) mice: effect of transgene expression.

The non-obese diabetic (NOD) mouse is a good model of insulin-dependent diabetes mellitus. Autoreactive T cells may play a fundamental role in disease initiation in this model, while disregulation of such cells may result from an abnormal thymic microenvironment. Diabetes is prevented in NOD mice by direct introduction of an E alpha d transgene (NOD-E) or a modified I-A beta chain of NOD origin (NOD-PRO or NOD-ASP). To investigate if disease pathology in NOD mice, protection from disease in transgenic NOD-E and NOD-PRO and partial protection from disease in NOD-ASP can be attributed to alterations in the thymic microenvironment, immunohistochemical and flow cytometric analysis of the thymi of these mouse strains was studied. Thymi from NOD and NOD-E mice showed a progressive increase in thymic B-cell percentage from 12 weeks of age. This was accompanied by a concomitant loss in thymic epithelial cells with the appearance of large epithelial-free areas mainly at the corticomedullary junction, which increased in size and number with age and contained the B-cell clusters. Such thymic B cells did not express CD5 and were absent in CBA, NOD-ASP and NOD-PRO mice as were the epithelial cell-free spaces, even at 5 months of age. Therefore the mechanisms of disease protection in the transgenic NOD-E and NOD-ASP/NOD-PRO mice may differ if these thymic abnormalities are related to disease.

Animals↗
PubMed1994

Reduced galactosyltransferase mRNA levels are associated with the agalactosyl IgG found in arthritis-prone MRL-lpr/lpr strain mice.

MRL-lpr/lpr strain mice have defectively glycosylated IgG. This may be related to the rheumatoid arthritis (RA)-like disease that occurs in these mice, because a similar glycosylation defect is seen in human subjects with RA. Whilst it is known that this defect is associated with reduced activity of the beta-1,4-galactosyltransferase (beta-1,4-GalTase) enzyme, the cause of this reduced activity is at present unknown. We have therefore examined the molecular genetics of beta-1,4-GalTase in MRL-lpr/lpr mice. Using 10 different restriction endonucleases we found no evidence for a polymorphic variant of the gene in glycosylation-defective mice. However, the level of mRNA for beta-1,4-GalTase was lowest in the MRL-lpr/lpr mice, the strain with the most poorly galactosylated IgG of the four strains examined. Thus, the reduced level of IgG oligosaccharide galactosylation found in MRL-lpr/lpr strain mice appears to be related to either an altered transcriptional level of, or altered mRNA stability for, beta-1,4-GalTase in lymphocytes from these mice.

Animals↗
PubMed1994

[Handling of organ donors].

Patients suffering from complete destruction of the brain and brain stem are the most common source of organs for transplantation purposes. However, as the lack of such organs is currently the most limiting factor regarding the scope of transplantation treatment, it is of the utmost importance that all potential donor organs are well maintained.

Brain Death↗
PubMed1994

A comparative evaluation of three transfection procedures as assessed by resistance to G418 conferred to HEPG2 cells.

Three commonly used transfection techniques (electroporation, calcium phosphate precipitation and scrape loading) and a novel procedure combining the latter two methods were evaluated and conditions optimised for successful transfection of human HepG2 cells with plasmid DNA incorporating a mouse MHC Class I gene and a selectable marker (neomycin transferase gene) conferring resistance to G418. While transfection with linear DNA by scrape-loading gave satisfactory results, transfer of cloned circular DNA by electroporation, calcium phosphate precipitation or a combined use of scrape-loading and calcium phosphate gave best results for HepG2 cells.

Animals↗
PubMed1993

RFLP analysis of the MHC class III region defines unique haplotypes for the non-obese diabetic, cataract Shionogi and the non-obese non-diabetic mouse strains.

The non-obese diabetic (NOD) mouse strain which spontaneously develops diabetes is a model for human Type 1 (insulin-dependent) diabetes mellitus. At least one of several genes controlling diabetes in the NOD mouse has been mapped to the MHC. Although previous experiments have implicated the MHC class II genes in the development of the disease, the existence of other MHC linked susceptibility genes has not been ruled out. In order to identify these susceptibility genes we have further characterized the MHC haplotype of the NOD mouse and two non-diabetic sister strains, the non-obese non-diabetic (NON) and cataract Shionogi (CTS). We have examined the mouse MHC class III region for the presence of homologous genes to 17 newly isolated human MHC class III region genes (G1, G2, G4, G6, G7a/valyl-tRNA synthetase, HSP70, G8, G9, G10, G12, G13, G14, G15, G16, G17 and G18). We detect unique hybridizing DNA fragments for 16 of the 17 genes in six inbred mouse strains (NOD, NON, CTS, B10, BALB/c and CBA/J) indicating that this part of the H-2 region is similar to the human MHC class III region. Using a panel of restriction enzymes we have defined RFLPs for 6 (G2, G6, HSP70, G12, G16, G18) of the 16 cross-hybridizing probes. The RFLPs demonstrate that NOD, NON and CTS mouse strains each have a distinct MHC haplotype in the MHC class III region.

Animals↗
PubMed1992

[Organ donation from recently deceased patients. Experiences from a donor hospital and suggestions for handling potential organ donors and their relatives].

Homologous organ transplantation using organs from patients suffering complete destruction of the brain and brain stem is a major achievement in modern medicine. The care of potential organ donors and their relatives is complex and very demanding for the medical team and nursing staff. In Norway the law sets very clear criteria (documentation of total irreversible brain and brain stem injury) for performing donation. As a rule consent from the family is asked for, although not legally required. This article deals with the problems related to the treatment of potential organ donors. We give practical guidelines for medical staff on how to prepare the patient and his/her family, with emphasis on the human and psychosocial aspects. Preservation of the donor and the organs is not discussed.

Decision Making↗
PubMed1992

[Burns].

Extensive burns are severe, life-threatening injuries. Cutaneous burns are often accompanied by injury to inhalation, leading to severe pulmonary problems with a high rate of mortality. Published reports on series of burn patients state that in 2-5% of all (burn) cases, cutaneous thermal injury was accompanied by mechanical injuries such as fractures, closed head injuries, or blunt injuries to chest and abdomen. The care of the burn is often made difficult by concomitant orthopaedic injury, and in a multiple trauma victim, the burn itself often complicates diagnosis and treatment. It is important to recognize all injuries as soon as possible. The article briefly discusses practical considerations when treating patients with multiple injuries including cutaneous burns and/or inhalation injury. After initial resuscitation and stabilization these patients should be transferred to a specialized treatment facility for burns. As a rule, open surgical reduction and fixation of fractures should be carried out no later than 48 hours after the injury.

Burns↗
PubMed1992

Altered course of visceral leishmaniasis in mice expressing transgenic I-E molecules.

Previous studies had shown that the outcome of infection with Leishmania donovani was exquisitely sensitive to the influence of the major histocompatibility complex. In this study, we have examined the course of infection in non-obese diabetic (NOD) and NOD-E-3 mice, the latter expressing an I-E molecule as a result of transgenic introduction of the wild-type Ed alpha gene. Introduction of this transgene significantly altered the course of infection allowing for enhanced parasite multiplication in the viscera from day 14 to day 28. This was associated with both a delayed and reduced tissue granulomatous response in NOD-E-3 mice. In vitro, spleen cells from these mice produced equivalent levels of interferon (IFN)-gamma during the early phase of infection but this originated from populations having a different balance of T cells subsets. In NOD mice CD8+ T cells contribute substantially to the total levels of IFN-gamma produced, but in transgenic mice the contribution from this subset is significantly decreased. This is reflected in a reduction in the proportion of Leishmania-specific CD8+ T cells, which could only partially be accounted for by deletion of V beta 5- and V beta 3-expressing CD8+ T cells in NOD-E-3 mice. This study highlights the impact of the introduction of a class II gene product on disease outcome and unexpectedly on the functional potential of CD8+ T cells.

Animals↗
PubMed1992

Analysis of the T cell receptor (TcR) regions in the NOD, NON and CTS mouse strains define new TcR V alpha haplotypes and new deletions in the TcR V beta region.

We have analyzed the T cell receptor (TcR) V alpha and TcR V beta regions in the spontaneous mouse model for insulin-dependent diabetes mellitus, the NOD mouse, and compared it to the regions in the two sister strains, the NON and CTS strains. Based on restriction fragment length polymorphism analysis the TcR V alpha region in the NOD mouse is essentially identical to that of the SJL/J strain. In contrast both the NON and CTS strains have a unique TcR V alpha haplotype. Whereas the NOD and NON strains apparently contains all the TcR V beta genes, the CTS mouse has three deletions in the V beta region. Our analysis does not give any indications for the diabetic phenotype of the NOD mouse.

Animals↗