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Biomedical subjects

M B Nielsen

Publications and source records attributed to M B Nielsen.

At least 37 records · Page 2Linked to original sources
PubMed1999

Increased vaccine-specific T cell frequency after peptide-based vaccination correlates with increased susceptibility to in vitro stimulation but does not lead to tumor regression.

Although in vitro sensitization assays have shown increased melanoma Ag (MA)-specific CTL reactivity after vaccination with MA peptides, clinical responses have been uncommon. This paradox questions whether data obtained from the in vitro stimulation and expansion of T cells lead to an overestimation of the immune response to vaccines. Using HLA/peptide tetramer (tHLA), we enumerated MA-specific T cell precursor frequency (TCPF) directly in PBMC from 23 melanoma patients vaccinated with gp100:209-217(210M) (g209-2M) peptide. Vaccine-specific TCPF was higher in postvaccination PBMC from seven of seven patients treated with peptide alone and four of five patients treated with peptide plus IL-12 (range of postvaccination TCPF, 0.2-2.4% and 0.2-2.5%, respectively). The increased TCPF correlated with enhanced susceptibility to in vitro stimulation with the relevant epitope. Paradoxically, no increase in postvaccination TCPF was observed in most patients who had been concomitantly treated with IL-2 (1 of 11 patients; range of postvaccination TCPF, 0.02-1.0%), a combination associated with enhanced rates of tumor regression. The lack of increase in TCPF seen in these patients corresponded to inability to elicit expansion of vaccine-specific T cells in culture. This study shows that a peptide-based vaccine can effectively generate a quantifiable T cell-specific immune response in the PBMC of cancer patients, though such a response does not associate with a clinically evident regression of metastatic melanoma.

CD8-Positive T-Lymphocytes↗
PubMed1999

[Knee alloplasty and working ability. The significance of knee alloplasty for working ability of patients who were working prior to surgery].

The effect of a total knee arthroplasty (TKA) on maintaining or restoring working ability for patients who preoperatively still were in active employment has not previously been reported. Between February 1989 and December 1990 a total of 926 patients (1024 knees) had the same type of TKA (AGC-2000) implanted at 14 different Danish hospitals. The patients were followed prospectively. Sixty-two patients (6.7% of the total material) were preoperatively registered as being still engaged in active employment. Follow-up after three years included 51 of these patients (with 62 knees). Fifty-eight percent were still working after three years compared to 79% after the first postoperative year. Only eight out of the 21 who quit their job during the follow-up period stated knee-trouble as being the direct cause. The most common reason for stopping work was ordinary age-determined pension. We found no correlation between the amount of occupational knee-load and the relative risk of not being able to continue working. Thus, four out of five patients who are employed preoperatively will generally be able to return to the same job within a year after a TKA.

Adult↗
PubMed1999

Effectiveness of active physical training as treatment for long-standing adductor-related groin pain in athletes: randomised trial.

BACKGROUND: Groin pain is common among athletes. A major cause of long-standing problems is adductor-related groin pain. The purpose of this randomised clinical trial was to compare an active training programme (AT) with a physiotherapy treatment without active training (PT) in the treatment of adductor-related groin pain in athletes. METHODS: 68 athletes with long-standing (median 40 weeks) adductor-related groin pain--after examination according to a standardised protocol--were randomly assigned to AT or PT. The treatment period was 8-12 weeks. 4 months after the end of treatment a standardised examination was done. The examining physician was unaware of the treatment allocation. The ultimate outcome measure was full return to sports at the same level without groin pain. Analyses were by intention to treat. FINDINGS: 23 patients in the AT group and four in the PT group returned to sports without groin pain (odds ratio, multiple-logistic-regression analysis, 12.7 [95% CI 3.4-47.2]). The subjective global assessments of the effect of the treatments showed a significant (p=0.006) linear trend towards a better effect in the AT group. A per-protocol analysis did not show appreciably different results. INTERPRETATION: AT with a programme aimed at improving strength and coordination of the muscles acting on the pelvis, in particular the adductor muscles, is very effective in the treatment of athletes with long-standing adductor-related groin pain. The potential preventive value of a short programme based upon the principles of AT should be assessed in future, randomised, clinical trials.

Adolescent↗
PubMed1999

Thymus size in preterm infants evaluated by ultrasound. A preliminary report.

PURPOSE: To sonographically evaluate the thymic size in preterm infants. MATERIAL AND METHODS: In 6 healthy infants, born in gestational weeks 34-37, and 6 infants born in weeks 24-32, the thymic volume estimate (the thymic index) was assessed. The measurements were compared to the estimates calculated from the prediction model for neonates. RESULTS: The slightly preterm infants fit the prediction model. In cases where the results failed to fit into the model, it was adjusted in order to cover lower birth rates. The extremely preterm infants initially had a very low thymic index but, when healthy, they reached the normal range. CONCLUSION: With the knowledge of the birth weight it is now possible to predict the thymic size in healthy infants weighing 2,070 g or more.

Birth Weight↗
PubMed1999

Thymus size in infants from birth until 24 months of age evaluated by ultrasound. A longitudinal prediction model for the thymic index.

PURPOSE: To do a follow-up sonography assessment of the thymic size in infants at an age of 24 months, and to create a longitudinal prediction model for the thymic index covering all ages from birth to 24 months. MATERIAL AND METHODS: Of 37 infants examined in an earlier investigation, 34 attended a 24-month follow-up examination. The thymic index, a volume estimate, was assessed by sonography and compared to clinical variables, breast-feeding status and illness. The longitudinal prediction model was based on data throughout 2 years. RESULTS: There was no significant relation between the thymic index and the clinical variables, breast-feeding status or illness at 24 months. An overall test for the effect of breast-feeding status at 4 months for infants from 0-24 months was significant, as was the actual body length of the infants from 0-8 months. Prediction models were estimated. CONCLUSION: Based on a 24-month longitudinal sonography study, prediction models are presented whereby the thymic size, as an index, can be predicted at all times from birth to 24 months of age.

Child Development↗
PubMed1998

[Pericarditis and inflammatory bowel disease].

Extraintestinal manifestations of ulcerative colitis and Crohn's disease are well described in the literature. These may be diagnosed before, concomitantly or after the diagnosis of the specific type of inflammatory bowel disease. Between 25% and 36% of patients with either type of IBD will have at least one extraintestinal manifestation. Pericarditis and myocarditis are rare, but potentially serious complications. We report one such case.

Adult↗
PubMed1998

Peptides derived from self-proteins as partial agonists and antagonists of human CD8+ T-cell clones reactive to melanoma/melanocyte epitope MART1(27-35).

The self-peptide MART1(27-35) derives from the melanocyte/melanoma protein Melan A/MART1 and is a target epitope of CD8+ T cells, commonly recovered from tumor-infiltrating lymphocytes of HLA-A2.1+ melanoma patients. Despite their prevalence in such patients, these CTLs generally appear to be ineffective in mediating tumor regression in vivo. We have noted previously that numerous peptides from both endogenous and foreign proteins are similar to MART1(27-35) and, potentially, are capable of productively engaging the T-cell receptors of patient-derived CTLs. This observation raised the question of whether CTLs in vivo might encounter self-peptide analogues of MART1(27-35) that lack full agonist activity, perhaps to the detriment of the antitumor CTL response. This possibility was evaluated using cloned, patient-derived CTLs with a panel of self-derived natural analogues of MART1(27-35) in assays for cytolysis, cytokine release, and phosphorylation of T-cell receptor signaling constituents. Several peptides were identified as partial agonists, capable of eliciting cytolysis and/or release of cytokines tumor necrosis factor-alpha and IFN-gamma but not interleukin 2. Several other peptides showed antagonist behavior, effectively inhibiting cytolysis of MART1(27-35)-pulsed targets, but did not inhibit killing of cells prepulsed with a synthetic, heteroclitic variant of MART1(27-35). Some of these antagonists also had lasting effects on interleukin 2 secretion by CTLs under experimental conditions involving sequential exposure to ligands. Together, these observations suggest that encounters with self-peptide analogues of MART1(27-35) may contribute to the peripheral maintenance of these CTLs, while ultimately impairing the efficacy of this antitumor T-cell response.

Antigens, Neoplasm↗
PubMed1998

Staphylococcus enterotoxin A modulates interleukin 15-induced signaling and mitogenesis in human T cells.

T cells expressing the appropriate T-cell receptor Vbeta chain proliferate in response to Staphylococcus enterotoxin A (SEA) pulsed antigen-presenting cells (APC), whereas other T cells do not (SEA "non-responders"). Activated human T cells express MHC class II molecules that are high affinity receptors for SEA. Here we show that, in the absence of APC, SEA induces a profound inhibition of IL-15-driven proliferation in MHC class II+, human SEA-"responder" T-cell lines. In contrast, proliferation induced by phorbol esther (PMA) was enhanced by SEA. The inhibitory effect on cytokine-mediated mitogenesis correlates with an inhibition of IL-2Rbeta expression and ligand-induced tyrosine phosphorylation of IL-2R. Cyclosporin A (CyA), an inhibitor of the protein phosphatase (PP2B) calcineurin, strongly inhibits the SEA-induced modulations of cytokine receptor expression. Moreover, CyA inhibits both the anti-mitogenic effect of SEA on cytokine-induced proliferation and the pro-mitogenic effect of PMA. In contrast, inhibitors of PP1, PP2A, protein kinase C (PKC), phosphatidyl-inositol-3-kinase (PI-3K) and mammalian target of rapamycin (mTOR) are unable to inhibit the effects of SEA. In a SEA "non-responder" T-cell clone obtained from the affected skin of a patient with psoriasis vulgaris, SEA does not inhibit IL-2Rbeta expression and IL-15-driven proliferation. On the contrary, SEA enhances IL-15- and IL-2-induced proliferation via a CyA-sensitive pathway in this T-cell clone. In conclusion, the present data show that (i) SEA selectively inhibits IL-15- (but not PMA-) mediated proliferation in SEA "responder" T cells, (ii) SEA enhances cytokine-driven growth in psoriasis T cells with a "non-responder" phenotype, and (iii) crosstalk between SEA receptors and the IL-15R (and IL-2R) pathway is mediated via a PP2B-dependent and PP1/PP2A-, PKC-, PI-3 kinase- and mTOR-independent pathway in human T-cell lines.

Cell Division↗
PubMed1998

Staphylococcal enterotoxin-A directly stimulates signal transduction and interferon-gamma production in psoriatic T-cell lines.

Bacterial superantigens such as staphylococcal enterotoxin-A (SEA) have been implicated in the pathogenesis of psoriasis vulgaris. Major histocompatibility complex (MHC) class II molecules are high affinity receptors for SEA, and T cells found in psoriatic skin lesions express high levels of MHC class II. Here we address the question of whether SEA can directly activate psoriatic T cells in the absence of professional antigen-presenting cells. We show that SEA induces i) tyrosine phosphorylation of several proteins, ii) downregulation of the T-cell receptor (TCR), and iii) production of interferon-gamma (IFN-gamma), but not autocrine mitogenesis in CD8-positive T clones obtained from skin lesions of a patient with psoriasis vulgaris. Psoriatic T cells do not respond to SEA molecules if mutations are introduced in the TCRbeta- or in both the two MHC class II alpha- and beta-binding sites of SEA. Mutations in only one of the two MHC class II binding sites of SEA has different effects on T-cell activation. Thus, SEA molecules with a mutation in the MHC class II beta-binding site induce protein tyrosine phosphorylation, but not IFN-gamma production or co-stimulation of cytokine-mediated proliferation. In contrast, SEA with a mutation in the MHC class II alpha-binding site induces IFN-gamma and a qualitatively changed tyrosine phosphorylation profile. Both mutations delete the co-stimulatory effect on cytokine-mediated proliferation. This suggests that both MHC class II binding sites are involved in the autopresentation of SEA by psoriatic T cells. In conclusion, we provide evidence that SEA directly activates MVHC class H-positive psoriatic T-cell lines to produce IFN-gamma, a key cytokine in the pathogenesis of psoriasis vulgaris.

Antigen-Presenting Cells↗
PubMed1997

Significant association between simple renal cysts and arterial blood pressure.

OBJECTIVE: To test the hypothesis that there is an association between simple renal cysts and arterial blood pressure (BP). PATIENTS AND METHODS: The study comprised a review of the case-notes of 115 patients (mean age 67.7 years, range 31-91) in whom renal cyst(s) was an incidental ultrasonographic finding, and 115 age- and sex-matched control patients. The notes were reviewed without knowledge of the origin or treatment. RESULTS: The systolic and diastolic BP were significantly higher in patients with a cyst(s) than in control patients (P = 0.031 and P = 0.0034; mean difference 6.9 mmHg and 5.0 mmHg, respectively). In those aged 30-70 years, the presence of one or more simple renal cysts increased the risk of having a diastolic BP > or = 95 mmHg from seven in 58 to 17 in 58 patients (P = 0.038). CONCLUSION: The association between simple renal cysts and higher arterial BP probably arises from underlying renal disease causing both. Occasionally it is possible that renal ischaemia caused by cyst expansion, and therefore increased renin release, generates the elevation in BP. If so, methods to identify such cysts should be developed.

Adult↗
PubMed1997

Sonographic measurement of thymic size in healthy neonates. Relation to clinical variables.

PURPOSE: To assess the variation in thymic size in healthy neonates by sonography and to study the possible correlation to clinical variables. MATERIAL AND METHODS: A study was made of 149 healthy term infants, at less than one week of age. The size of the thymus was assessed by sonography as a volume estimate, the thymic index. This index was compared to sex, weight, length, gestational age, and level of perinatal asphyxia of the infant. T-cell subsets (percentages of CD4 and CD8 receptor-positive T-lymphocytes in peripheral blood) were determined in 83 of the infants and compared to the sonographic thymic index. RESULTS: The thymic index varied between 4 and 29, and was positively correlated to the weight of the infant (p = 0.0003). There was no correlation to sex, length, gestational age or slight perinatal asphyxia. We found no correlation between the size of the thymus and the CD4 percentage, the CD8 percentage, or the CD4/CD8 ratio. CONCLUSION: The size of the thymus in healthy neonates as measured by sonography is significantly correlated to the weight of the infant. For a given weight of an infant it is possible to predict the normal range of thymic size.

Anthropometry↗
PubMed1997

Thymus size evaluated by sonography. A longitudinal study on infants during the first year of life.

OBJECTIVE: To use sonography in a follow-up study aimed at assessing the size of the thymus in healthy infants, and to search for a possible relation to clinical variables, breast-feeding status, and illness. MATERIAL AND METHODS: Forty-seven healthy infants were examined as neonates and re-examined at 4 months of age. Thirty-seven of the infants were also re-examined at 8, 10, and 12 months of age. The thymus size was measured with the sonographic thymic index used as a volume estimate. The correlations between the thymic index and the sex, weight, length, illness, and breast-feeding status of the infants were analysed. RESULTS: At birth the median thymic index was 12 (range 4-29). At 4 months the median thymic index was 28 (range 12-83). The thymic index was positively correlated to the body length of the infant and to its breast-feeding status (p < 0.0001). At 8 months the median thymic index was 29 (range 6-55) and most of the variation could be explained by the length of the infant (p = 0.0018, r = 0.50). At 10 months the median thymic value had decreased to 19 (range 9-49), and at 12 months to 17 (range 7-53). Infants exclusively breast-fed during the first 4 months of their lives had a larger thymic index at 10 months than formula-fed infants (p = 0.0024). Infants with fever episodes from 10 to 12 months had a smaller thymic index at 12 months (p = 0.0241). CONCLUSION: The thymus size in healthy infants increases from birth to 4 and 8 months of age and then decreases. Most of the individual variation can be explained by breast-feeding status and body size, and to a lesser extent by illness. We propose statistical models by which the normal variation/distribution of the thymic size can be estimated in infants up to one year of age.

Age Factors↗
PubMed1996

[Angiotensin-converting enzyme inhibitors and anesthesia].

The increasing usage of ACE-inhibitors in the treatment of hypertension and chronic heart failure may increase the incidence of adverse anaesthetic occurrences. Four such cases are described. In two of these cases, the patient reacted with severe hypotension when general anaesthesia was supplemented with epidural bupivacaine. Another patient suffered a heart fatality after severe hypotension in conjunction with the administration of a spinal anaesthetic. Finally, one patient suffered sudden fatal pulmonary oedema after completion of uneventful general anaesthesia, possibly due to late resumption of ACEI-treatment. The cases are discussed in detail, with particular reference to the possible underlying mechanisms. Preoperative discontinuation of ACEI-treatment is controversial. We present some of the issues involved. Most authors lean towards continuing ongoing treatment, even though there is firm evidence that this increases the risk of hypotensive episodes due to hypovolaemia, arguing that such events may be predicted and antagonized with fluid therapy.

Aged↗
PubMed1996

Chemically induced sarcomas from nude mice are more immunogenic than similar sarcomas from congenic normal mice.

To detect possible differences in immunogenicity between tumors induced in T cell-deficient mice and phenotypically normal congenic mice, 16 sarcomas, 8 having developed in nude BALB/c mice and 8 having developed in congenic normal (nu/+) mice, were transplanted to normal BALB/c recipients and the rates of rejection or acceptance were registered. The 16 tumors were chosen randomly from a panel of 39 sarcomas induced with 0.5% or 0.1% 3-methylcholanthrene and maintained as cell lines in culture. Out of the tumors originating from nude mice, 66% were rejected by the normal BALB/c recipients, while only 30% of the tumors originating from normal mice were rejected. Tumors with short induction times from normal mice were more readily accepted than tumors with long induction times. Tumors originating from nude mice had significantly longer mean latency times after transplantation to both normal and nude recipients than tumors originating from normal mice. Contrary to what has been reported by others, there was no correlation between the rejection rates of the individual tumors and their Kd, Dd or Ld major histocompatibility complex (MHC) class I surface expression as measured by flow cytometric analysis of cultured tumor cells. The Kd, Dd and Ld proteins of the transplanted tumor lines were analyzed by isoelectric focusing for the occurrence of mutations resulting in altered charge of the MHC protein. No such mutations were found, ruling out MHC mutations of that kind as the source of immunogenicity in the cell lines used in these experiments. Our results suggest the existence of a T cell-mediated selection in the original tumor cell mass of tumors induced in normal mice, adapting the tumor to growth in a host with a functional T cell system, but apparently there is no connection between this loss of immunogenicity and loss of MHC class I expression.

Animals↗
PubMed1996

Sonographic measurement of the thymus in infants.

A new method of measuring the size of the thymus in infants less than 1 year of age is presented. The width of the thymus was measured in a transverse image while the area of the largest lobe was assessed in a longitudinal image. The thymic index was then defined as the product of these two values. Intra- and interobserver variation analysis were performed in 23 infants. Each infant was scanned alternately by both of two radiologists, and later the same day the measurements were repeated. The mean differences between the first and second measurements (intraobserver variation) were -0.25 (2 SD 7.56) and -1.13 (2 SD 10.80), respectively, for the two observers. The mean difference between the first measurements of the two observers (interobserver variation) was 1.47 (2 SD 9.39). In a postmortem study of 12 infants the thymic index measured by sonography showed an acceptable correlation to the actual volume (c = 0.80) and weight (c = 0.87) of the thymus. In conclusion, our sonographic estimate of the volume of the thymus, the thymic index, in infants under 8 months of age seems to be easy, reliable and reproducible.

Anthropometry↗
PubMed1996

Decreased thymus size in formula-fed infants compared with breastfed infants.

The objective of this research was to investigate if breastfeeding affects the size of the thymus. Ultrasound assessment of the thymic index (a volume estimate) at birth and age 4 months in 47 healthy infants born in the hospital were used. History of feeding mode, body size and illness were registered. At 4 months the geometric mean thymic index (range) was 38.3 (16.2-83.2) in exclusively breastfed infants (n = 21), 27.3 (15.6-50.0) in partially breastfed infants (n = 13) and 18.3 (12.2-32.6) in formula fed infants (n = 13; p = 0.0001, ANOVA). This finding was independent of weight, length, sex and previous or current illness. There was no significant difference in mean thymic index at birth between the three feeding groups and mean thymic index had increased in all three groups from birth to 4 months. For the formula-fed infants it seems that the thymus remains large for a period and then decreases in size after breastfeeding has been terminated. We conclude that the thymus is considerably larger in breastfed than in formula-fed infants at the age of 4 months. The cause of this difference is unknown but human milk contains many immune modulating factors that might cause this effect.

Analysis of Variance↗
PubMed1996

Changes in the anal sphincter with age. An endosonographic study.

PURPOSE: To describe the changes in the endosonographic appearance of the anal sphincter muscles with age. MATERIAL AND METHODS: Fifty subjects (age range 22-85 years) with no history of anorectal disease or surgery were studied with anal endosonography. The thickness of the internal and external anal sphincter was registered and correlated to age. For the internal sphincter, which is often asymmetric, the maximum and minimum thicknesses were measured at any part of the circumference (except anteriorly for anatomic reasons) and also in the lateral positions. RESULTS: A significant positive correlation with age was found for all maximum, minimum, and average internal sphincter thicknesses. Moreover, the echogenicity of the internal sphincter changed with age as the sphincter muscle became more echogenic. There was no significant correlation between external sphincter thickness and age. CONCLUSION: Knowledge of the normal variation of the internal sphincter thickness with age is important since endosonography may be used to identify patients with hypertrophy of the internal sphincter. Currently, we consider maximal thicknesses above 4 mm to be abnormal in patients under 50 years of age, whereas in patients aged at least 50 years thicknesses of 5 mm or more are considered abnormal.

Adult↗