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Biomedical subjects

N Grunnet

Publications and source records attributed to N Grunnet.

At least 73 records · Page 4Linked to original sources

A perifusion system for cultured hepatocytes.

A perifusion system for primary cultures of hepatocytes is described. The system accommodates 20 rotated petri dishes (60 mm) and allows individual medium composition and sampling for each dish. Cell number and insulin (15 pM to 7.7 nM) were stable in the system for at least 24 h. The dose-response relationship for induction by insulin of glucokinase and pyruvate kinase was shifted to the left by a factor of 9 and 5, respectively, as compared to conventional, stationary cultures. The system is useful for studies at low and/or constant concentrations of substrates, hormones, growth factors, etc., with monolayers of cells having a high metabolic capacity.

Animals↗

Prospective study of anticardiolipin antibodies in immunized and untreated women with recurrent spontaneous abortions.

OBJECTIVE: To investigate whether active leukocyte immunization increases levels of anticardiolipin antibodies in women with recurrent spontaneous abortions. To assess the impact of anticardiolipin antibodies on pregnancy outcome in these women. DESIGN: Patients who had received various treatments in an ongoing randomized trial were studied prospectively. SETTING: A department of clinical immunology investigating women with recurrent spontaneous abortions from all over Denmark. PATIENTS: Eighty-nine patients with unexplained recurrent spontaneous abortions whose pregnancies had been completed during the course of the trial. INTERVENTIONS: After randomization, 44 patients were actively immunized with husband's or third party leukocytes, and 27 patients received placebo. Eighteen patients received anticoagulation therapy in pregnancy. MAIN OUTCOME MEASURES: Changes in levels of immunoglobulin (Ig)M class and IgG class anticardiolipin antibodies after active immunization. Frequency of new miscarriages in patients who were positive or negative for anticardiolipin antibodies. RESULTS: Neither IgM nor IgG anticardiolipin antibodies changed significantly after active immunization (P greater than 0.2). The interim results of the immunization trial showed a success rate of 68% in the treated group versus 56% in the placebo group (not significantly different). Relative risk of miscarriage in anticardiolipin antibody-positive patients compared with anticardiolipin antibody-negative patients was 1.3 (95% confidence interval 0.7 to 2.2; P = 0.4) in the combined study groups. CONCLUSIONS: Patients eligible for active immunization did not exhibit significant changes in anticardiolipin antibody levels subsequent to the treatment. The treatment did not seem to provide any overall benefit with respect to pregnancy outcome. Prospectively, the risk of miscarriage in patients positive for anticardiolipin antibodies was not significantly increased.

Abortion, Habitual↗

Intravenous immunoglobulin treatment of women with multiple miscarriages.

Eleven women who had previously experienced four to eight unexplained fetal losses (median 6.0 fetal losses/woman) were treated in their next pregnancy with individualized doses of pooled intravenous immunoglobulins. Nine women (82%) delivered healthy infants subsequent to the treatment. Prior to treatment, the pregnant patients had a significantly (P less than 0.05) increased median level of complement C3 neodeterminants in the blood compared with a group of 33 normal first trimester pregnant women. This may be a sign of increased turnover of complement in these women.

Abortion, Habitual↗

Studies of RFLP-inferred HLA-DR-DQ haplotypes in Danish women with recurrent fetal losses.

Results of HLA-DR and -DQ typing by RFLP in 152 unrelated women with at least 3 unexplained fetal losses were compared with those of 210 normal controls. The overall distribution of DR-DQ phenotypes did not differ significantly between patients and controls. In a subgroup of 59 patients having had at least 4 fetal losses, a significantly higher number of patients than controls were DRw17,DQw2-positive (RR = 2.9, pcorrected less than 0.02). DR-DQ haplotypes which carry DQB1 alleles encoding an amino acid other than aspartic acid at codon 57 in the second exon (non-Asp57 haplotypes) have been reported to confer susceptibility to several immunologically-mediated diseases. We found that the total frequency of non-Asp57 haplotypes (other than DR7,DQw2 which has unique features) was significantly increased in patients (50.0%) compared with controls (39.3%) (p less than 0.005). In the total group of patients and in the group with at least 4 fetal losses, 22.4% and 32.2% respectively were homozygous non-Asp57/non-Asp57 compared with 13.3% among controls (RR = 1.9, p less than 0.025 and RR = 3.1, p less than 0.001, respectively). The results suggest that DRw17,DQw2 confers susceptibility to suffer recurrent fetal losses. However, it is possible that the HLA-associated susceptibility may be primarily conferred by DQ molecules lacking aspartic acid at codon 57 in the DQ beta chain.

Abortion, Habitual↗

Study of the birthweight of parents experiencing unexplained recurrent miscarriages.

OBJECTIVE: To examine birthweight and preterm birth rates in couples with unexplained recurrent miscarriages. DESIGN: A case control study. Birth data of couples with recurrent miscarriages were obtained from midwife records. Time and sex-matched births from the same records served as controls. SETTING: A Regional Hospital in Denmark. SUBJECTS: 79 singleborn women with recurrent miscarriages and 60 of their male partners comprised the main study groups. Two control groups comprised 474 female and 360 male singleborn infants who survived day 7 postpartum. MAIN OUTCOME MEASURES: Mean birthweight in the two main study groups and in subgroups with histories of 3, 4 and greater than or equal to 5 miscarriages. RESULTS: The mean birthweight of the women with recurrent miscarriages was 3265 g (SE 70) and in female controls 3414 g (SE 23) (P less than 0.025). The 17 women with five or more miscarriages had a mean birthweight of 2991 g (SD 140) (P less than 0.001 compared with controls). Of the women in the study group 10.8% were born preterm compared with 2.9% of the controls (P = 0.01). The mean birthweight of the male partners in the study group, 3470 g (SE 68), did not differ significantly from that of 3504 g (SE 31) in the male controls (P less than 0.5). CONCLUSIONS: Women suffering unexplained recurrent miscarriages have on average had a significantly lower than normal birthweight themselves, whereas this was not observed in their male partners. This points towards the existence of a birthweight-reducing trait associated with recurrent miscarriages, the trait being manifest only in the woman.

Abortion, Habitual↗

Long-term supplementation with n-3 fatty acids, II: Effect on neutrophil and monocyte chemotaxis.

The effect of a daily supplement with 4 g of n-3 polyunsaturated fatty acids (PUFA) for 9 months to 24 healthy volunteers on neutrophil and monocyte chemotaxis was studied using the under-agarose technique. Autologous serum and n-formyl-methionyl-leucyl-phenylalanine were used as chemoattractants. The effect after 9 months of supplementation with n-3 PUFA was also compared to results after short-term supplementation with n-3 PUFA for 6 weeks. Monocyte chemotaxis was reduced after 9 months of supplementation with n-3 PUFA to the same extent as after 6 weeks supplement. Neutrophil-directed migration towards chemoattractants was reduced after 9 months on fish oil, and this decrease was significantly greater than the decrease obtained after 6 weeks of supplementation. The spontaneous migration of neutrophils was significantly attenuated after 9 months compared to baseline and to 6 weeks. These findings lend support to a role for n-3 PUFA in the management of chronic inflammatory and atherosclerotic vascular diseases.

Adult↗

Phagocytic properties of granulocytes after intravenous injection of ioxaglate or iohexol.

To evaluate the influence of radiographic contrast media (CM) on human granulocytes, the ability of these cells to ingest latex particles after intravenous injection of ioxaglate and iohexol was investigated. Both CM inhibited the phagocytic properties of granulocytes; the inhibition was the most pronounced immediately after the injection, but inhibition was also observed 60 min after injection of ioxaglate. The inhibition 1 and 5 min after injection of CM was more pronounced after injection of ioxaglate than after injection of iohexol. However, this difference between the 2 CM was not significant. Significant inhibition of phagocytosis was found for mannitol solutions with osmolalities higher than 369 mOsm/l. Significant inhibition of phagocytosis was observed when granulocytes were isolated with either Hypaque/Ficoll or Percoll gradient centrifugation and then incubated with diatrizoate. Thus the ability of granulocytes to phagocytize latex particles was inhibited after i.v. injection of 50 ml ioxaglate or iohexol. Part of this inhibition may be due to hyperosmolality.

Granulocytes↗

Immunologic observations in close relatives of two sisters with mammary Burkitt's lymphoma. Mammary Burkitt's lymphoma in sisters.

In a sibship of four sisters, two had Burkitt's lymphoma localized to the breast. Their pretreatment Epstein-Barr virus (EBV) serology were not examined. No EBV genome was demonstrated in the tumors using an in situ hybridization technique. The mother showed an abnormal antibody response to EBV infection consisting of elevated IgA and IgG antibody titers to viral capsid antigen (VCA) and high IgG antibody titer to early antigen. Furthermore, one of the two healthy sisters showed elevated IgG antibody titer to VCA. The EBV serology is mimicking the findings in female carriers of the X-linked lymphoproliferative syndrome.

Adolescent↗

Tumour necrosis factor alpha and interleukin-2 in plasma from rheumatoid arthritis patients in relation to disease activity.

Tumour necrosis factor alpha (TNF alpha) and interleukin-2 (IL-2) are potential immunological mediators of pathogenetic changes in rheumatoid arthritis. We measured the concentrations of TNF alpha and IL-2 in plasma from 2 groups of patients suffering from rheumatoid arthritis (RA). One group had high and one had low disease activity. In addition, in connection with steroid treatment in the high disease activity group, TNF alpha was significantly increased in plasma from RA patients with high disease activity compared with those of low disease activity (p = 0.0009). Furthermore, TNF alpha decreased significantly in relation to steroid medication, parallel to clinical improvement (p = 0.016). All IL-2 concentration measurements were within the estimated normal range. The increased TNF alpha plasma levels in patients with rheumatoid arthritis with high disease activity, might result from activated white mononuclear cells in the inflamed joints. This might, in part, support the theory that TNF alpha is a possible mediator of pathogenetic changes known to occur in rheumatoid arthritis.

Arthritis, Rheumatoid↗

Increased frequency of HLA-DRw14b(w6)-associated RFLP in Greenlanders of Eskimo origin.

HLA-DR typing by the restriction fragment length polymorphism (RFLP) technique of 42 Greenlanders living in northern Jutland, Denmark, revealed a phenotype frequency of 33.3% for HLA-DRw14b(w6), which is significantly different from the frequency of 0.0% observed among 98 Danes of Caucasian origin. When comparing the two populations, the frequency of other HLA-DRB allogenotypes show insignificant variations. Since HLA-DRw14b(w6) is carried by approximately one-third of the Greenlanders tested, this allogenotype may serve as a useful marker in further anthropological and immunogenetic studies.

Denmark↗

Turpentine- and fibrin-induced pleuritis in nude mice. Histopathological, cellular and biochemical changes.

Turpentine was injected into the right pleural cavity of nude immune-incompetent mice, causing a temporary irritative exudative pleuritis. A transient occurrence of so-called rheumatoid arthritis cells was observed in the pleural fluid together with parallel characteristic biochemical changes. In similar experiments in nude mice, however, immunization followed by intrapleural application of bovine fibrin showed irritative "dry" pleuritis without the presence of rheumatoid arthritis cells. This is in contrast with previous results from similar experiments done using normal mice. The conclusion from the present experiments is that in nude immune-incompetent mice only the non-immunological, turpentine-induced pleuritis will generate cellular and biochemical changes typical of the rheumatoid disease in patients, while the fibrin-induced pleuritis fails to show similar changes. This suggests that the rheumatoid-like pleural changes described in the present experiments in nude mice have a non-immunological basis.

Animals↗

Non-capsulated Haemophilus influenzae in the genital flora of pregnant and post-puerperal women.

Non-capsulated Haemophilus influenzae may cause neonatal septicaemia. Genital carriage of this pathogen was studied in 3 mothers of infected neonates and in 2 pregnant women in the first trimester. A carrier state in 2 of the females was terminated by antibiotic therapy after 3 and 7 months, respectively. A previous carrier had no recurrence of H. influenzae in a subsequent pregnancy. A survey of 544 parturient women revealed a carrier rate of 1.8/1,000 (95% confidence limits: 0.1-11). Carriage of non-capsulated H. influenzae is thus rare, and pregnant women may be successfully treated in order to reduce the risk of neonatal infection. There was no evidence of immunodeficiency in women with non-capsulated H. influenzae in the genital tract.

Adult↗

HLA or HLA-linked genes reduce birthweight in families affected by idiopathic recurrent abortion.

HLA typing was performed in 49 families, each containing at least one woman with a history of unexplained recurrent spontaneous abortion (RSA), and reproductive histories were recorded for the siblings. Abortion rate in sisters sharing two HLA haplotypes with the proband was significantly (p less than 0.01) increased, whereas abortion rates of brothers' wives seemed independent of the brothers' degree of HLA sharing with the proband. Birthweights of offspring of both the sisters and the brothers decreased with increasing HLA haplotype identity between the sibling and the proband (p = 0.05). The mean birthweight of infants of siblings sharing both parental haplotypes with the proband was 3158 g which was significantly (p less than 0.02) less than the average birthweight in Denmark (3417 g). Significantly (p less than 0.05) decreased mean birthweight in infants of brothers who were HLA-identical with the proband suggested that the disposition to growth retardation could be inherited with HLA also through the male gametes. It has been shown that, in their few successful pregnancies, women with RSA bear infants with a birthweight which is approximately 300 g less than normal. The present study demonstrated that the two obstetrical conditions, RSA and retarded fetal growth, share common genetic markers: HLA. It is suggested that HLA or HLA-linked genes causing growth retardation in fetuses are part of the putative complex of genes involved in the pathogenesis of recurrent abortion.

Abortion, Incomplete↗