Biomedical subjects
M Thomsen
Publications and source records attributed to M Thomsen.
[Toxic shock syndrome. A case of a child with burns].
A case of the toxic shock syndrome (TSS) in a burnt (scalded) child is presented. TSS is a condition most frequently associated with menstruating women using tampons. In recent years, however, increased knowledge of the syndrome has led to an increase in the number of reported cases associated with other clinical situations. The non-menstrual cases are most frequently observed in young persons many of whom are children. TSS is due to infection with toxin-producing S. aureus. TSS-toxin-1 is apparently the most important among toxins. The fatality rate has been reported to be as high as 15%, so recognition of the syndrome and institution of the correct treatment are of utmost importance. By means of an easy and rapid test, it is possible to detect if the strain of S. aureus is TSST-1-producing. The test is now available and employs passive latex agglutination. The sensitivity and specificity are high and, if clinical signs of TSS are present, a positive test result will support the diagnosis in 94% of alle positive cases.
Development of the treatment of partial skin thickness burns since the Second World War: an overview.
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[Powerlessness and frustration].
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Corecognition of HLA-A1 and HLA-DPw3 by a human CD4+ alloreactive T lymphocyte clone.
We have generated an alloreactive proliferative T cell clone that only is stimulated by HLA-DPw3+ antigen presenting cells (APC) that at the same time carry HLA-A1. The T cell clone is CD4+, and the proliferation is blocked by anti-DP monoclonal antibodies and not by antibodies towards other class II or towards class I molecules. Family studies show that APC with A1 and DPw3 on different haplotypes (trans) are able to stimulate the clone, and an HLA recombinant family gives evidence that the class I-carrying part of the haplotype is necessary for stimulation to occur. Stimulation is also observed with mixtures of APC expressing DPw3 and APC expressing A1, and likewise, DPw3+ APC become stimulatory when preincubated with supernatants from A1-positive cells. Our studies suggest that major histocompatibility complex (MHC) class I peptides presented by class II are allostimulatory and that APC can process MHC molecules that presumably are presented as allele-specific peptides in the context of other MHC molecules. We hypothesize that presentation of MHC peptides by MHC molecules constitutes an important part of alloreactive phenomena in vivo and in vitro.
Evolution of the HLA-DR1 gene family. Structural and functional analysis of the new allele "DR-BON".
The molecules of the MHC are highly polymorphic and involve in Ag presentation; their striking genetic polymorphism allows probable interactions with a large variety of antigenic fragments when these are presented to the TCR. It is therefore of interest to explore the extent of this polymorphism and the mechanisms of its generation. We have studied the class II HLA-DR blank allele DR-BON that has been previously defined by MLR, restriction fragment length polymorphism, and two-dimensional gel electrophoresis. A cDNA library was constructed from a DR-BON homozygous typing cell and cDNA corresponding to DR alpha- and DR beta-chains were sequenced. By comparison with other known alpha- and beta-chain sequences it is shown that the alpha-chain is invariant and the beta-chain differs from DR1 by only six nucleotides, clustered in the third variable region with three amino acid changes at position 67, 70, and 71. The short DNA stretch of sequence encoding the 67-71 region is also present in other DR alleles: DR4/Dw10, DRw13, and some DRw11 specificities. Therefore we propose that a gene conversion-like event has occurred between the DRB1 *0101 (DR1/Dw1) gene and one of these three DRB1 genes. Extensive typing has been performed with a DR-BON-specific 17-mer oligonucleotide. Cross-hybridization with other genes than the ones expected from DNA sequence comparison was not observed. A selected panel of DR-BON reactive T cell clones shows three patterns of reactivity. Some clones are strictly DR-BON specific; some cross-reacted with DRw13 and a few cross-reacted with other haplotypes. The role of different epitopes of the third variable region of HLA-DR beta chain in allo-reaction is discussed.
Analysis of HLA-DP in HLA-DR/GLO recombinant families and in the population of south-western France.
The existing estimates of the recombination fraction between DR and DP are quite variable and often based on anecdotal observations. We have estimated the DR/DP crossover frequency on the basis of families typed for HLA markers and GLO. The frequency of DR/GLO crossing over was 8.7% (23/264 informative meioses), maternal recombinations being about twice as frequent as paternal ones. Of 17 DR/GLO recombinant families typed for DPw1-6, DP was informative in 11 (13 recombinations) but only one of these gave rise to a DR/DP crossover. According to these data the DR/DP recombination fraction is below 1%, in contrast to some earlier published materials. HLA-DR/DP haplotypic associations on 127 informative Caucasoid haplotypes have been evaluated. In agreement with previous studies, DR3 was positively associated with DPw1 and, in addition, DR7 was found to be positively associated with DP-blank (not DPw1-6). The rare DPw6 allele is possibly associated with the DR4, Dw14 allele. The DR-DP haplotype profiles suggest other associations which might become significant if larger materials are tested. The frequency of DP alleles in a random material (N = 201) was found to be in accordance with most of the previously published frequences on European Caucasoids with DPw4 as the predominating frequency (gene frequency 40%) and a blank frequency of 27%.
Characterization of PPD-specific T-cell lines generated in type I (insulin-dependent) diabetic and healthy individuals.
The particular susceptibility to insulin-dependent diabetes mellitus (IDDM) conferred by HLA-DR3,4 heterozygosity has been suggested to be an effect of transcomplementation of HLA class II molecules. To test this hypothesis of special IDDM-specific hybrid determinants and to evaluate the T-cell repertoire towards a specific antigen in IDDM patients we generated a total of 352 PPD-specific T-cell lines by the soft-agar cloning technique and studied their restriction by HLA class II molecules. Of these lines, 227 were from nine IDDM patients, of whom six were DR3,4 heterozygotes, and 125 from 10 healthy controls. Forty-six T-cell lines elicited specific responses in at least two experiments and in addition to T-cell lines demonstrating class-II-restricted PPD specificity, lines with an alloreactivity occurred. HLA-DQ-restricted PPD-specific T-cell lines were not identified and a possible DP restriction (DPw2) was only observed with one line. These data indicate that PPD is preferentially presented to T cells in the context of HLA-DR/Dw. Presentation of PPD by hybrid molecules in IDDM patients or by IDDM-specific class II epitopes recognized by the T-cell lines was not demonstrated. By restriction fragment length polymorphism analysis using a probe for the joining region of the T-cell receptor gamma gene, T-cell lines generated by the soft-agar cloning technique were found to be oligoclonal. It is concluded that soft-agar cloning should be followed by subsequent limiting dilution in order to assure monoclonality. Different preparations of antigen-presenting cells (APC) were tested. In several cases the T-cell lines were not able to respond to PPD presented by Epstein-Barr-virus-transformed lymphoblastoid cell lines (LCL). It was demonstrated that lipopolysaccharides (LPS) of E. coli potently reduce the proliferative response of antigen-specific and alloreactive T cells when T-cell-depleted peripheral blood mononuclear cells (E- cells) were used as APC, whereas only limited inhibition was observed when LCL were used as APC in the presence of LPS. This effect of LPS is suggested to be mediated by increased prostaglandin secretion by monocytes among the E- cells since indomethacin abolished the effect of LPS. This observation may have implications for T-cell cloning procedures since we have found that most commercially available culture media are heavily contaminated with endotoxin.
Recombinations in the HLA system.
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Clinical features and pathology of burns.
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[Microbiological findings in patients with burns. An analysis of 253 patients admitted to the Copenhagen Burn Center in 1985].
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[International Nurses' Day. Obstetrical nursing of great importance for a nation's health].
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The susceptibility to insulin-dependent diabetes mellitus is associated with C4 allotypes independently of the association with HLA-DQ alleles in HLA-DR3,4 heterozygotes.
In the genetically homogeneous Danish population, 27 HLA-DR3,4 heterozygous patients with insulin-dependent diabetes mellitus (IDDM) and 19 DR3,4 heterozygous controls without family history of IDDM were investigated for HLA-region markers and Gm and Km immunoglobulin allotypes. The aim was to define susceptibility factors for IDDM development other than HLA-DR using a number of techniques: lymphocytotoxicity (HLA-DR and DQ antigens), cellular methods (Dw and DP typing), restriction fragment length polymorphism (DQ alleles), electrophoresis and immunofixation (BF and C4 allotypes), and passive hemagglutination inhibition (Gm and Km immunoglobulin allotypes). The complement allotype C4A3 and the HLA-DQw8 (DQw3.2) antigen were found in all of the patients, whereas this was the case for only 8 of the 19 controls (P = 6 x 10(-6)): five lacked C4A3, five others lacked DQw8, and one of the controls lacked both of these factors. Fourteen of the patients had the complement allotype C4B3 versus three of the controls (P = 0.01). Previously reported family studies suggest that these alleles are part of the following haplotype: B15, BFS, C4A3, C4B3, DR4, Dw4, DQw8, and these factors were found together in ten of the patients versus one of the controls (P = 0.01). The markers usually associated with DR3 did not show significant differences between IDDM patients and controls, and the non-HLA markers studied showed no significant deviation from what was expected. In addition to the susceptibility factor DQw8, the study suggests the existence of susceptibility genes for IDDM near the complement C4 genes on DR4-carrying haplotypes.(ABSTRACT TRUNCATED AT 250 WORDS)
Patulin immunotoxicology: effect on phagocyte activation and the cellular and humoral immune system of mice and rabbits.
Patulin is a mycotoxin frequently found in rotten apples or molded corn. We have investigated the effect of sublethal doses of patulin on the immune system in mice and rabbits. A significant suppression of the chemiluminescence response of peritoneal leucocytes was observed in both species. Mouse spleen lymphocytes showed a decrease in absolute number, most pronounced for the B-cell population whereas the Ts population showed a relative increase after patulin treatment. The mitogenic response to PHA, Con A and, in particular, PWM was also depressed by patulin. This was paralleled by decreasing serum immunoglobulin levels in the mice and rabbits. The immunosuppressive effect of patulin is reversible and is probably due to interaction with cellular free SH groups since the action of patulin can be circumvented, at least partially, by the prior administration of cystein. Under natural circumstances, patulin may constitute a health risk for animals.
Colonization priority among Staphylococcus aureus strains--correlation with phage-type.
We have studied the distribution of phage-type patterns among strains of Staphylococcus aureus isolated from patients in a burns unit. From 51 patients the same phage-type was isolated from succeeding swabs during the observation period. In 20 patients new types were introduced, but the original strain remained. In 23 patients the first strain was replaced by one other strain, in eight patients two or more. Strains of type 95 seemed to have a high colonization priority, whereas strains of group III had a low one. In 1986 phage-typing was performed on two or more S. aureus strains from the same patient, in 4561 instances. Recurrence of strains of the same phage-type pattern was demonstrated in 70% of the patients when the first and the fourth sample were compared. The "newer epidemic" strains of phage-type 95 and of the 94,96 complex had the highest percentage of recurrence (more than 80%) when adjacent samples were compared, and 68-69% when the first and the fourth sample were compared. The good colonization capacity of these strains might be one of the explanations why they occur frequently today although they are resistant only to penicillin.
Tamm Horsfall glycoprotein interferes with bacterial adherence to human kidney cells.
The effect of Tamm Horsfall protein (THP) of 18 healthy subjects and 14 diabetics on adherence of Escherichia coli (06:K13) 2699 strain to human kidney cells (HUK) was studied. Adhesion of bacteria (without additions: 100 bacteria per cell) was reduced dose-dependently by THP, half maximal inhibition occurring with 250 micrograms THP ml-1. Maximal inhibition (-84% at 1000 micrograms ml-1) exceeded inhibition by alpha-methyl-mannoside (36% at 50 mM), was specific (not reproduced by other glycoproteins, e.g. ovalbumin, mucin or thyroglobulin) and reversible (abolished by washing THP off HUK cells). Anti-adherence property of THP was not abolished by neuraminidase treatment. No significant difference of anti-adherence activity of THP was found between controls and diabetics, despite altered carbohydrate composition of THP in diabetes.