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Biomedical subjects

N Rasmussen

Publications and source records attributed to N Rasmussen.

At least 37 records · Page 2Linked to original sources
PubMed1995

Tumour-infiltrating lymphocytes mediate lysis of autologous squamous cell carcinomas of the head and neck.

Tumour-infiltrating lymphocytes (TIL) and tumours from six patients with squamous cell carcinomas of the head and neck (SCCHN) were investigated. The six tumours all expressed major histocompatibility complex (MHC) class I antigens both in vivo and as tumor cell lines grown in vitro. In addition, the cancer cells either overexpressed the tumour-suppressor gene product p53 or harboured human papilloma virus 16/18 (HPV). The TIL were expanded in vitro in the presence of interleukin-2, immobilised anti-CD3 mAb and soluble anti-CD28 mAb. Expanded TIL cultures contained both CD4+ and CD8+ T cells, but generally contained few CD56+CD3- cells of the natural killer (NK) phenotype. CD8+ T cells dominated the individual TIL cultures from five of the six patients and showed significant autologous tumour cell lysis. In TIL cultures derived from four of these tumour-reactive TIL cultures, killing could be partially blocked by an anti-MHC class I mAb. TIL cultures reacting with autologous tumour cells also showed strong TCR/CD3-redirected cytotoxicity when assayed against hybridoma cells expressing anti-TCR/CD3 mAb as well as natural-killer(NK)-like activity. A number of TIL cultures devoid of autologous tumour cell lysis were capable of lysing the natural-killer(NK)-sensitive K562 cell line suggesting that the SCCHN cells themselves are resistant to NK-like lysis. In conclusion, TIL cultures from head and neck carcinomas contain T cells which, upon expansion in vitro, can lyse autologous tumour cells in a MHC-class-I-restricted fashion. Thus, the results of the present study document that carcinomas of the head and neck in some patients are infiltrated by cytotoxic T cell precursors potentially capable of rejecting the autologous tumour.

Adult↗
PubMed1995

Staphylococcus aureus meningitis: a review of 28 consecutive community-acquired cases.

From 1966 to 1989 a total of 1,830 cases of bacterial meningitis were recorded at the Department of Infectious Diseases, Rigshospitalet, Denmark. Staphylococcus aureus meningitis accounted for 44 (2.4%) of these cases. Among these, 28 cases were classified as community-acquired S. aureus meningitis. The mortality rate for these cases was 43%. A retrospective study of clinical features and parameters in these community-acquired cases showed the following conditions to be associated with a high mortality risk: advanced age, an underlying condition requiring artificial ventilation, cardiovascular disease and immune deficiencies. At admission, more than 75% of the patients had fever, nuchal rigidity and decreased consciousness. In 57% of cases the focus for the S. aureus infection was endocarditis, pneumonia or skin infections. All the patients had complications due to the meningitis, the major one being insufficient respiration. Autopsy performed in 9 of the 12 fatalities showed endocarditis in 5, pneumonia in 4, and pyelonephritis in 2. All of the brains examined at autopsy showed cerebral and subarachnoid hemorrhage.

Adolescent↗
PubMed1994

In vivo infiltration of mononuclear cells in squamous cell carcinoma of the head and neck correlates with the ability to expand tumour-infiltrating T cells in vitro and with the expression of MHC class I antigens on tumour cells.

A series of 18 head and neck squamous cell carcinoma biopsies, 6 primary and 12 recurrent, were investigated for tumour-infiltrating mononuclear cells with monoclonal or polyclonal antibodies. Our results suggest that the number of T cells at the tumour edge in vivo correlates well with their ability to expand in vitro in the presence of high-dose interleukin-2 (2000 U/ml). High MHC class I antigen expression on tumour cells was found to be positively correlated with p53 overexpression, suggesting that p53-derived peptides, wild-type or mutated ones, presented by MHC class I antigens, are potential targets for MHC-restricted cytotoxic T cells in head and neck squamous cell carcinomas. However, lack of correlation between peritumoural T cell infiltration in vivo and T cell expansion in vitro, on the one hand, and p53 overexpression on tumour cells, on the other hand, suggests absence of p53-peptide-specific T cells in the patients. Eight out of ten expanded tumour-infiltrating lymphocyte (TIL) cultures showed T-cell-mediated cytotoxicity. "Promiscuous" cytotoxic T cell activity against the natural-killer-cell-sensitive K562 target cell line was observed in three out of ten TIL expansion cultures.

Animals↗
PubMed1994

Statistical model estimating the occurrence of otitis media from temporal bone pneumatization.

In order to investigate the relationship between the pneumatization of temporal bones and the occurrence of otitis media in Greenlandic Inuit, 36 Greenlandic Inuit were examined by radiography of the temporal bones. The pneumatized cell area was measured planimetrically. All subjects answered a questionnaire on infectious middle ear disease (IMED), and an objective otologic examination was performed. Nine persons of 34 (26%) reported IMED in childhood, and there was IMED reported in all pneumatized areas below 400 mm2. Based on bilateral area measures, a polychotomous logistic regression model was applied. The occurrence of IMED was shown to be associated with smaller areas, and unilateral IMED was associated with pronounced asymmetry. The model has enabled risk assessment, and 8 persons were designated by the model as having had IMED with a sensitivity of 67% (confidence interval 30% to 93%) and a specificity of 92% (confidence interval 74% to 99%). When the model was applied to a historical anthropological Inuit material from 1700 to 1800 AD, 6 of 56 crania were designated as having had IMED. This method has improved the accuracy of estimating the occurrence of IMED in ancient populations.

Adolescent↗
PubMed1993

The value of indirect immunofluorescence and solid phase techniques for ANCA detection. A report on the first phase of an international cooperative study on the standardization of ANCA assays. EEC/BCR Group for ANCA Assay Standardization.

This study describes the results of phase I of an international effort to develop and standardize assays for the detection of anti-neutrophil cytoplasmic antibodies (ANCA). 12 sera, four of which were selected for their potential to cause problems in the detection of various ANCA specificities, were analyzed in the standard indirect immunofluorescence (IIF) test and in ELISAs for ANCA routinely performed in the seven participating laboratories. The IIF methodology differed with respect to the dilution of the serum being screened and the concentration of the conjugate used. Results from sera with high ANCA titers were similar, although the quantitative values could not be compared. In sera containing rheumatoid factor and anti-nuclear antibodies (ANA), ANCA-unrelated staining patterns were observed. Six antigen preparations were used in ELISA for the detection of cANCA. In ELISA with purified proteinase-3 all three cANCA sera were positive, but not anti-myeloperoxidase (MPO) or anti-lactoferrin (LF) positive sera. The other assays were less sensitive or gave inconsistent results. Various preparations of purified MPO and LF used in ELISA were readily recognized by anti-MPO and anti-LF positive sera. From this study it can be concluded that the IIF test, although performed with different methods, shows comparable results using strongly positive sera. In general solid phase assays for cANCA detection are not well standardized and need improvement although the purified proteinase-3 ELISA is possibly an exception. MPO and LF can be used in ELISA procedures for the detection of pANCA-related antibodies.

Antibodies, Antineutrophil Cytoplasmic↗
PubMed1993

Cellular immune responses and pathogenesis in c-ANCA positive vasculitides.

Very little is known about the cellular immune response in c-ANCA (classical anti-neutrophil cytoplasm antibodies) positive vasculitides or Wegener's granulomatosis (WG). The present review is mainly based on published and unpublished observations of the Cattegat Study Group of Wegener's Granulomatosis. Immunohistochemical examinations of nasal biopsies from untreated patients with active WG revealed the presence of substantial amounts of cells belonging to the immune system (CD3+, CD4+, CD8+, CD20+, CD38+ and CD68+). The IgG response of peripheral mononuclear cells from untreated WG patients to PWM and EBV stimulation was significantly depressed when examined by the reverse haemolytic plaque forming cell assay. T lymphocyte proliferation was observed by in-vitro stimulation with extract of human neutrophil alpha granules, containing the autoantigen for c-ANCA, proteinase-3, only in patients with c-ANCA and active disease. Electron microscopy of biopsies from nasal lesions in untreated patients with active WG did not show structural abnormalities of the organelles of macrophages, giant cells or epithelioid cells. It is concluded that the immune response leading to c-ANCA production involves the full spectrum of immunocompetent cells normally engaged in IgG production to a foreign antigen. This would be in agreement with a theory of cross reactivity of proteinase-3 with a microbial antigen as a pathogenetic mechanism.

Antibodies, Antineutrophil Cytoplasmic↗
PubMed1993

Cerebrovascular changes following administration of gammaglobulins against substance P or calcitonin gene related peptide in monkey with subarachnoid haemorrhage.

Cerebrovascular changes after intrathecal (ith) administration of gammaglobulins against substance P (SP) or calcitonin gene-related peptide (CGRP) were investigated before and following a simulated subarachnoid haemorrhage (SAH) in the squirrel monkey. The SAH was produced by injection of homologous blood into the interpeduncular fossa and the cisterna magna. The gammaglobulins were given both prior to the blood injections and daily in 5 days post-SAH. The effect of the gammaglobulins was examined by angiography pre-SAH and at 10 min and at 6 days post-SAH, i.e. the time points for maximal acute and late spasm in the present model. Cerebral blood flow (CBF) was measured under general anesthesia at day 6 post-SAH with an autoradiographic technique. Five of nine animals treated with CGRP antigammaglobulin died from respiratory failure. Four animals received SP antigammaglobulin and two control animals received normal globulin. SP antigammaglobulin per se had no effect on baseline arterial diameter, while CGRP antigammaglobulin significantly reduced the diameter of the arteries. SP antigammaglobulin prevented the occurrence of acute spasm and significantly reduced the degree of late spasm. Moreover, the reduction in CBF noted in the control SAH animals was significantly reduced. In contrast, CGRP antigammaglobulin treatment had no effect on the degree of spasm and did not cause any change in CBF as compared to controls. The finding that CGRP but not SP antigammaglobulin significantly reduces the arterial diameter in conjunction with our previous demonstration that a post-, but not preganglionic trigeminal lesion reduces the baseline arterial diameter, indicates that CGRP could be the transmitter involved in a peripheral axon reflex. The function of SP might be as a neurotransmitter conveying information to the brainstem. The transmitter role is supported by the effect of SP antigammaglobulin impairing SP containing neurons and, in that way, mimicking a bilateral trigeminal rhizotomy.

Analysis of Variance↗
PubMed1992

[Behçet's syndrome: an unusual cause of genital erosion].

A case of incomplete mucocutaneous Behçet's disease is presented. In spite of weekly to monthly attacks of genital pain for fifteen years, this diagnostic entity had been ignored. We wish to emphasize that Behçet's disease may be the cause of otherwise unexplained genital erosions. A set of clinical criteria according to an international study group serves to establish the diagnosis. Treatment is controversial. This case has been successfully treated with systemic tetracycline for more than six months.

Adult↗
PubMed1992

Impaired 1,25-dihydroxyvitamin D production in pregnancy-induced hypertension.

The aim of the study was to evaluate the calcium metabolism in pregnancy-induced hypertension. Fifty-three women with pregnancy-induced hypertension were studied and the control groups comprised 20 women with uncomplicated pregnancies in the third trimester and 51 non-pregnant women, respectively. The mean serum concentrations of 1,25-dihydroxyvitamin D in women with pregnancy-induced hypertension was low (38.6 +/- 21.4 pg/ml) compared to women with uncomplicated pregnancies (91.0 +/- 18.2 pg/ml), but comparable to levels in non-pregnant women (32.2 +/- 11.9 pg/ml). Mean serum levels of PTH and ionized calcium were comparable in women with pregnancy-induced hypertension and women with uncomplicated pregnancies. In conclusion, the calcium metabolism in pregnancy-induced hypertension was changed compared to uncomplicated pregnancies with respect to the serum concentration of 1,25-dihydroxyvitamin D.

Adult↗
PubMed1992

Anti-neutrophil cytoplasm antibodies, anti-GBM antibodies and anti-dsDNA antibodies in glomerulonephritis.

The diagnostic potential of assays detecting anti-neutrophil cytoplasm antibodies (ANCA), anti-GBM antibodies and anti-dsDNA antibodies was evaluated by examining sera from time of admission in a consecutive series of 455 patients with biopsy verified primary or secondary glomerulonephritis (GN). ANCA were classified into c- and p-ANCA by indirect immunofluorescence (IIF) and ELISAs using alfa-granule extract, proteinase-3, myeloperoxidase (MPO), elastase and lactoferrin. C-ANCA was virtually confined to 64 patients with systemic small vessel vasculitis, 66-74% being c-ANCA positive. P-ANCA against MPO, seen in 47 patients, segregated through many diagnostic categories of primary and secondary severe GN. ANCA against lactoferrin and elastase were rare. Anti-dsDNA positive patients constituted 57% of the 44 ANA-positive patients with systemic lupus erythematosus. It is concluded that the IIF and ELISAs for anti-proteinase-3, anti-MPO, anti-dsDNA and anti-GBM have an acceptable performance and are useful in the primary diagnostic work-up of patients suspected for secondary GN as the majority of such patients will be classified by these assays.

Antibodies, Antineutrophil Cytoplasmic↗
PubMed1991

Glucose tolerance and incidence of pancreatic islet cell antibodies in pregnancy in women with thyroid autoantibodies.

The prevalence of pancreatic islet cell antibodies (ICA) and complement fixing ICA (CF-ICA) and the effect of pregnancy of glucose tolerance was studied in 3 groups of women. One group had thyroid autoantibodies in serum detected in early pregnancy and subsequent development of postpartum thyroiditis (PPT), another group had thyroid autoantibodies without signs of PPT and the third group did not have thyroid autoantibodies or PPT. In the women with thyroid autoantibodies and PPT, ICA were found in one of 12 women (8%, 95% confidence limits 0-38%). In the group with thyroid autoantibodies without PPT, ICA were found in three of 27 women (11%, 2-29%), whereas two of 20 women without thyroid autoantibodies had ICA (10%, 1-32%), N.S. Where present, serum ICA levels were very low and similar in early pregnancy and 6 months postpartum. CF-ICA were only found in two women with thyroid autoantibodies without signs of PPT. In all groups glucose tolerance was impaired in pregnancy when compared to postpartum despite an increased insulin response to glucose ingestion. In pregnancy, however, glucose tolerance was more impaired in the women with thyroid autoantibodies and subsequent PPT, than in the women without thyroid autoantibodies. Postpartum glucose tolerance was similar in all groups. It is concluded, that the presence of thyroid autoantibodies in early pregnancy or development of PPT is not accompanied by an increased prevalence of islet cell antibodies, but women with thyroid autoantibodies and subsequent PPT have a significantly more reduced glucose tolerance in late pregnancy than women without thyroid autoantibodies.

Adult↗