PubMed HealthSearch

Biomedical subjects

T Lund

Publications and source records attributed to T Lund.

At least 19 recordsLinked to original sources

[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

[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

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

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

Ankylosing spondylitis and HLA-B27: restriction fragment length polymorphism and sequencing of an HLA-B27 allele from a patient with ankylosing spondylitis.

Two groups of patients with ankylosing spondylitis (AS) from England and Poland were examined for restriction fragment length polymorphisms (RFLPs) associated with the disease. No preferential association was found between the 9.2 kb PvuII fragment in HLA-B27 positive patients with AS compared with HLA-B27 healthy subjects as had been previously reported. In the English group, however, a 14 kb PvuII fragment was more common in HLA-B27 positive subjects with AS than in normal controls. Also 4.6 and 3.7 kb PvuII fragments were more prevalent in subjects without AS than in the group with AS, but these results were confined to the English group. Furthermore, the sequence of an HLA-B*2705 gene isolated from a patient with AS was examined, and no significant differences were found compared with the sequence isolated from a healthy subject. There do not seem to be significant genetic differences in the coding or in the regulatory region in HLA-B27 alleles, in subjects with or without AS.

Alleles

The intronless mouse gene for the tissue specific splicing protein SmN is a processed pseudogene containing a stop codon after thirty-one amino acids.

The SmN protein is a component of small ribonucleoprotein particles which is closely related to the ubiquitously expressed splicing proteins SmB and B' but is expressed in only a small number of cells and tissues. We have isolated a mouse SmN-related sequence which lacks introns and contains multiple changes from the SmN cDNA sequence including a stop codon after thirty-one amino acids which would prevent it encoding functional SmN protein. This indicates that this intronless gene is a processed pseudogene and that the functional gene has yet to be isolated. In agreement with this southern blotting of mouse DNA with SmN probes reveals bands, additional to those derived from the pseudogene, which are characteristic of an intron-containing SmN gene. The relationship of the pseudogene to the functional SmN gene and to an intronless SmN-related sequence in the rat genome is discussed.

Amino Acid Sequence

Hip fractures in two health care regions in Finland in 1989: an analysis of treatment.

We studied prospectively the demographic data, fracture types and modes of treatment in 390 patients with acute traumatic hip fractures in two health care regions in Finland, the Middle Finland region and the Kymenlaakso region in 1989. In Middle Finland population (251,203 inhabitants) 199 patients with a hip fracture were admitted to two acute care hospitals, while 191 patients were admitted in Kymenlaakso (population 189,726) to four acute hospitals. There were no significant differences in the sex- and age-specific incidences between the two regions. In Middle Finland, 70% of the fractures were of the femoral neck, 28% were trochanteric and 2% subtrochanteric. The corresponding figures in Kymenlaakso were 57%, 38% and 5% (P < 0.05). In Middle Finland, 73% of the femoral neck fractures were treated primarily with a hemiendoprosthesis, 2% with primary total hip replacement and 25% by osteosynthesis. The corresponding figures in Kymenlaakso were 81%, 7% and 12% (P < 0.001). The mean duration of hospital stay was 14 days in Middle Finland and 21 days in Kymenlaakso (P < 0.01).

Adult

Metaphase-specific phosphorylations weaken the association between chromosomal proteins HMG 14 and 17, and DNA.

The high-mobility-group proteins HMG 14 and 17 have been isolated from human cells arrested in metaphase. The affinity between an unphosphorylated and two phosphorylated forms of these proteins, and DNA has been investigated using columns of single-stranded and double-stranded DNA. It was shown that the most phosphorylated forms had much lower affinity for single-stranded and double-stranded DNA compared to the unphosphorylated form present in interphase cells. The results are in accordance with the view that HMG 14 and 17 may dissociate transiently from chromatin during mitosis.

Chromatography, Liquid

High-mobility-group proteins P1, I and Y as substrates of the M-phase-specific p34cdc2/cyclincdc13 kinase.

All dividing cells entering the M phase of the cell cycle undergo the transient activation of an M-phase-specific histone H1 kinase which was recently shown to be constituted of at least two subunits, p34cdc2 and cyclincdc13. The DNA-binding high-mobility-group (HMG) proteins 1, 2, 14, 17, I, Y and an HMG-like protein, P1, were investigated as potential substrates of H1 kinase. Among these HMG proteins, P1 and HMG I and Y are excellent substrates of the M-phase-specific kinase obtained from both meiotic starfish oocytes and mitotic sea urchin eggs. Anticyclin immunoprecipitates, extracts purified on specific p34cdc2-binding p13suc1-Sepharose and affinity-purified H1 kinase display strong HMG I, Y and P1 phosphorylating activities, demonstrating that the p34cdc2/cyclincdc13 complex is the active kinase phosphorylating these HMG proteins. HMG I and P1 phosphorylation is competitively inhibited by a peptide mimicking the consensus phosphorylation sequence of H1 kinase. HMG I, Y and P1 all possess the consensus sequence for phosphorylation by the p34cdc2/cyclincdc13 kinase (Ser/Thr-Pro-Xaa-Lys/Arg). HMG I is phosphorylated in vivo at M phase on the same sites phosphorylated in vitro by H1 kinase. P1 is phosphorylated by H1 kinase on sites different from the sites of phosphorylation by casein kinase II. The three thermolytic phosphopeptides of P1 phosphorylated in vitro by purified H1 kinase are all present in thermolytic peptide maps of P1 phosphorylated in vivo in proliferating HeLa cells. These phosphopeptides are absent in nonproliferating cells. These results demonstrate that the DNA-binding proteins HMG I, Y and P1 are natural substrates for the M-phase-specific protein kinase. The phosphorylation of these proteins by p34cdc2/cyclincdc13 may represent a crucial event in the intense chromatin condensation occurring as cells transit from the G2 to the M phase of the cell cycle.

Animals

Characterization of pancreatic islet cell infiltrates in NOD mice: effect of cell transfer and transgene expression.

Insulin-dependent diabetes mellitus can be transferred into young irradiated non-obese diabetic (NOD) mice by spleen cells from a diabetic NOD donor. T cells (both L3T4+ and Ly-2+) enter the pancreas 2 weeks following transfer. They are present initially at peri-islet locations but progressively infiltrate the islet with accompanying beta cell destruction. The infiltrate is heterogeneous with respect to V beta usage. Inflammatory macrophages (Mac-1+, F4/80+) can be detected at peri-islet locations at 1 week after transfer and continue to be recruited during the disease process. Their presence at the initiation of disease suggests that their primary function may be autoantigen presentation. Increased expression of major histocompatibility complex (MHC) class I molecules is observed on both endocrine and exocrine tissue in areas of intra-islet infiltration. MHC class II and ICAM-1 expression was restricted to the cells constituting the inflammatory infiltrate. Expression of these molecules was not observed on beta cells implying that presentation of autoantigen by the beta cell itself does not play a role in the beta cell destruction in NOD mice.

Animals

Regulation of human growth hormone receptor gene expression by human growth hormone in a human hepatoma cell line.

We have investigated the effects of recombinant human growth hormone (r-hGH) on the expression of hGH-receptor in a human hepatoma cell line (HuH 7). Levels of hGH-receptor mRNA in HuH 7 cells treated with different doses of r-hGH were measured by means of an RNase protection assay. Treatment with r-hGH at physiological concentrations (12.5, 25 and 50 ng/ml) resulted in an increase in hGH-receptor mRNA levels within 1 h of addition of the hormone. A steady state was reached after 3-4 h and maintained for at least 48 h. In contrast, treatment with supraphysiological r-hGH concentrations (150 and 500 ng/ml) led to a down-regulation of hGH-receptor mRNA levels during the first 3 h after hormone addition followed by an increase in hGH-receptor mRNA levels thereafter. Nuclear run-off assays demonstrated that these changes in hGH-receptor mRNA levels were a result of changes in the rate of transcription of the hGH-receptor gene. Cycloheximide (10 micrograms/ml) did not affect these changes in hGH-receptor gene transcription significantly, indicating that they are mediated by pre-existing factors and do not require new protein synthesis. These data demonstrate that r-hGH specifically regulates the rate of transcription of the hGH-receptor gene in a human hepatoma cell line.

Blotting, Northern

A methodological note concerning long-term effect of treatment.

The long-term effect of treatment is defined as the score change produced directly and indirectly by the treatment during and after the treatment interval. Various instances of combinations of short-term effects, attained during the treatment interval, and of long-term effects are presented. Designs for measuring the short-term and long-term effects are sketched, and suggestions are given for distinguishing between these effects in six representative cases. A multiple-occasion measurement of the long-term effect is recommended.

Follow-Up Studies

Two metamodels of causal effects.

Two metamodels, termed Model S and Model V, are proposed for definition, measurement, and generalization of quantitative causal effects. The effect is defined as a part change in score in Model S and as a part change in variance in Model V. Two additional changes, total and remainder change, are defined. The latter is due to all other factors or variables than the cause, while total change is the sum of remainder and effect change. Furthermore, it is shown how contrafactual concepts, which imply that some parts of the study situation are supposed to be otherwise, enter into the metamodels. Casual effects are defined and measured in terms of non-contrafactual concepts, except that statistical induction includes contrafactual as well as non-contrafactual inferences. Non-statistical generalization involves both kinds of inferences. Contrafactual definitions are considered inadequate, and a contrafactual interpretation of statistical adjustment is unnecessary and should be replaced by a non-contrafactual one.

Adult

On the expression of HMG I protein in quiescent and proliferating human T lymphocytes.

The results demonstrate that the HMG I protein is expressed in human quiescent T lymphocytes and hence is not dependent upon proliferation or neoplastic transformation. Furthermore it has been found that the HMG I/histone H1 ratio increase about two-fold after activation with phytohemagglutinin and was about the same as in a number of proliferating human leukemia lymphoma T-cell lines.

Antibodies, Monoclonal

The metaphase specific phosphorylation of HMG I.

In vivo labelling of HeLa cells arrested in metaphase with [32P]-phosphate and in vitro phosphorylation of HMG I with the partially purified growth associated H1 kinase was used to study metaphase specific phosphorylation of HMG I. It was found that threonine 53 and 78 became phosphorylated. These amino acids are embedded in respectively the sequence PTPKR and TPGRK which are similar to the sequences phosphorylated by the growth associated H1 kinase.

Amino Acid Sequence

Prevention of insulin-dependent diabetes mellitus in non-obese diabetic mice by transgenes encoding modified I-A beta-chain or normal I-E alpha-chain.

Insulin-dependent diabetes mellitus (IDDM) is a disease with an autoimmune aetiology. The inbred non-obese diabetic (NOD) mouse strain provides a good animal model of the human disease and genetic analysis suggests that, as in man, at least one of the several genes controlling the development of IDDM is linked to the major histocompatibility complex. The NOD mouse does not express I-E owing to a deletion in the promoter region of the I-E alpha-chain gene, and the sequence of NOD I-A beta-chain in the first external domain is unique with His 56 and Ser 57 replacing Pro and Asp, respectively, at these positions. There has been considerable interest in the role amino acid 57 might have in conferring susceptibility to autoimmune diseases, including IDDM. The presence of a charged residue (such as Asp) at this position might affect the conformation of the peptide binding groove. But it could be assumed that Pro 56 gives rise to a different conformation of I-A beta-chain than does His 56. We therefore constructed transgenic NOD mice in which the transgene encoded a modified A beta nod with Pro 56, and studied its effect on the development of IDDM in this mouse strain. Previous studies have suggested that NOD mice expressing I-E as a result of the introduction of an I-E alpha-chain (E alpha) transgene are protected from the development of insulitis and hence IDDM. To explore further the protective effect of this molecule we constructed a second class of transgenic NOD mouse carrying an E alpha d transgene. Both transgenes protected the mice from IDDM, but this was not associated with a complete deletion of any T cells expressing commonly used T-cell receptor V beta genes.

Animals