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Biomedical subjects

B Nilsson

Publications and source records attributed to B Nilsson.

At least 343 records · Page 19Linked to original sources

Differential stability of recombinant human insulin-like growth factor II in Escherichia coli and Staphylococcus aureus.

Recombinant human insulin-like growth factor II (IGF-II), produced as a soluble extracellular fusion protein, was shown to be proteolytically degraded in Escherichia coli. In contrast, the fusion protein secreted from Staphylococcus aureus was stable and the full length product could be recovered by affinity chromatography. After site specific cleavage of the fusion protein, soluble IGF-II with biological activity was obtained without refolding procedures. These results demonstrate that a eukaryotic protein unstable in E. coli can be stabilized by expression in a Gram positive host. The full-length fusion protein from S. aureus was used to characterize the protease responsible for the degradation in E. coli. Biochemical and genetic analysis suggests a specific degradation by the outer membrane protease (OmpT).

Amino Acid Sequence↗

Influence of elective cesarean section and breech delivery on neonatal neurological condition.

Fifty-three infants born after elective cesarean section (CS), and 28 infants born vaginally in breech presentation were compared with 45 full-term controls. A quantitative neurological assessment consisting of 31 items was performed on days 1, 2 and 5 after birth. A tonus score, an excitability score and the number of optimal responses were calculated. A follow-up examination was done at 6 months of age, with a standardized neurological and developmental examination. The results showed that infants born after elective CS in both vertex and breech presentation had significantly reduced number of optimal responses during the first five days after delivery, compared to controls. They were more hypotonic and less excitable than the control infants during the first 2 days. There were no significant differences in neurological results between infants born after CS with general or epidural anaesthesia. The infants born in vaginal breech presentation showed no differences neurologically as compared to the controls on the first day. On days 2 and 5, however, they were less excitable and showed a reduced number of optimal responses. There were few differences in neurological condition between the infants born after elective CS and the infants born vaginally in breech presentation. Growth, psychomotor development and neurological status at 6 months did not differ significantly between the three groups. Our findings indicate that infants born after elective CS and vaginal breech presentation have a delayed neurological adaptation during their first days of life. These differences did not affect the physical well-being of the infants, which showed normal growth, neurology and development at the follow-up at 6 months of age.

Apgar Score↗

Interactions in the renal and biliary elimination of digoxin: stereoselective difference between quinine and quinidine.

The interactions between digoxin and quinine and quinidine that affect the renal and biliary clearances of digoxin were investigated in eight healthy subjects. Digoxin (0.5 to 0.75 mg/day) was given alone and with concomitant administration of quinine (750 mg/day) to reach a steady-state level. In four of the subjects, the study was repeated by administration of equimolar doses of the diastereoisomer quinidine together with digoxin, enabling a within-subject comparison of the effects of the two isomers on digoxin clearance. The biliary excretion of digoxin was studied by use of a modified duodenal marker perfusion technique. A marked reduction was found in the steady-state biliary clearance of digoxin from control value 134 +/- 57 ml/min (mean +/- SD) to 87 +/- 39 ml/min during treatment with quinine (p less than 0.05) and from 95 +/- 24 to 55 +/- 27 ml/min during treatment with quinidine (p less than 0.01; n = 4). Quinidine reduced the renal clearance of digoxin (155 +/- 26 versus 110 +/- 21 ml/min) (p less than 0.05; n = 4), whereas quinine had no such effect (177 +/- 40 versus 185 +/- 53 ml/min; not significant). These findings explain the difference in magnitude between quinidine and quinine in regard to the interaction with digoxin and imply a different degree of stereoselectivity for these isomers in the renal and biliary secretory systems of digoxin.

Adult↗

A dual-affinity gene fusion system to express small recombinant proteins in a soluble form: expression and characterization of protein A deletion mutants.

A novel gene fusion system to express and purify small recombinant proteins in Escherichia coli has been constructed. The concept allows for affinity purification of soluble gene products by sequential albumin- and Zn2(+)-affinity chromatography. The dual-affinity system is well suited for expression of unstable proteins as only full-length protein is obtained after purification and proteins gain proteolytic stability in the fusion protein. Here we show that the dual-affinity approach can be used for the expression of various unstable derivatives of a single IgG-binding domain based on staphylococcal protein A. Analysis of the proteolytic stabilities and the IgG-binding properties of the different mutant proteins suggest that the model for the structure of an IgG-binding domain must be re-evaluated.

Base Sequence↗

A European multicenter study of chronic graft-versus-host disease. The role of cytomegalovirus serology in recipients and donors--acute graft-versus-host disease, and splenectomy.

A group of 466 leukemic bone marrow transplanted patients were reported from 17 European bone marrow transplantation teams. Of these, 285 survived more than 3 months and could be evaluated for chronic GVHD. The cumulative incidence of chronic GVHD was 32% two years after BMT. The following factors were statistically significantly associated with chronic GVHD in bivariate analysis: high donor and recipient age, splenecacute GVHD, pretransplant seropositivity to CMV among the recipients and the donors, and donor seropositivity to 3 or 4 different herpesviruses, compared with 0-2, prior to BMT. In multivariate analysis pretransplant recipient CMV seropositivity in combination with donor CMV seropositivity prior to BMT (P = 0.0006), a previous grade II-IV acute GVHD (P = 0.001), and splenectomy (P = 0.01) were significantly associated with chronic GVHD. Thus, in addition to acute GVHD, CMV immune donor cells may be triggered by latent CMV in the recipient, which may play a role in the triggering of chronic GVHD. The possible role of splenectomy in GVHD is also discussed.

Adolescent↗

Purification and characterization of IgG immunoconglutinins from patients with systemic lupus erythematosus: implications for a regulatory function.

The levels of IgG immunoconglutinins in plasma from patients with rheumatoid arthritis, systemic lupus erythematosus and primary biliary cirrhosis were monitored by ELISA. High levels of IgG immunoconglutinins were found mainly in plasma from patients with systemic lupus erythematosus. These immunoconglutinins bound to microtitre plate-fixed C3, C3b and C3c but poorly to C3d. This binding was inhibited by particle-bound C3b and iC3b but not by the corresponding soluble fragments. Furthermore, Western blot analysis revealed no immunoconglutinin-binding to reduced C3 peptides and no binding was shown to soluble C3 alpha and beta chain by ELISA. IgG immunoconglutinins were purified from three plasma specimens by affinity chromatography on activated thiol sepharose ATS/C3 fragments. Two immunoconglutinin preparations that preferentially recognize ATS-C3b, inhibited C5-convertase function by 50-100% while one immunoconglutinin that recognized ATS-C3d,g had no effect. The two former immunoconglutinins also inhibited all three factor I cleavages in C3 alpha chain but the latter inhibited only the third cleavage. None of the immunoconglutinins affected the binding of complement-coated anti-BSA/BSA complexes to CR1 (CD35) on human erythrocytes, but the two immunoconglutinins that inhibited all factor I cleavages also inhibited the factor I-induced release of anti-BSA/BSA complexes from CR1. The results show that immunoconglutinins recognize specific epitopes on bound C3 fragments and that they are able to modulate C3-mediated functions.

Antibody Specificity↗

Cardiovascular death after radiotherapy for benign bleeding disorders. The Radiumhemmet metropathia cohort 1912-1977.

Of 788 women treated with ionizing irradiation for benign bleeding disorders (metropathia) 308 (39%) died of cardiovascular disease. In a control group, consisting of 1219 women with metropathia who were not irradiated, 257 (21%) cardiovascular deaths occurred. Although the risk of cardiovascular death in the two studied cohorts compared with national death rates was only 0.92 (lower limit 0.82; upper limit 1.03) and 0.88 (lower limit 0.78; upper limit 0.99) respectively, it was found that women irradiated before the menopause (age 50 years) run a higher risk of cardiovascular death than the controls in the same age group and those irradiated after the menopause.

Adult↗

Tumour markers as prognostic aids in prostatic carcinoma.

Of 102 patients suffering from prostatic carcinoma, complete data on the serum concentration of 7 tumour markers were available from 90 patients, together with tumour grade, local stage and the presence or absence of skeletal metastases. The serum content of prostatic acid phosphatase, prostate specific antigen, neopterin, thymidine kinase, osteocalcin, C-reactive protein and tissue polypeptide antigen was measured. By means of Cox's regression and multivariate analysis the ability of these variables to predict prognosis, i.e. death from prostatic cancer, was studied. Neopterin appeared to be the most efficient marker, followed by tumour grade, thymidine kinase and prostate specific antigen. No other variable provided information of statistical significance. In multivariate analysis thymidine kinase performed best, followed by neopterin, tumour grade and prostate specific antigen. Several serum tumour markers reflect the biological activity of human prostate cancers and their value should be further explored. They may become useful in the management of individual patients.

Antigens, Neoplasm↗

Natural killer cell activity in monoclonal gammopathies: relation to disease activity.

Natural killer (NK) activity and NK-related cell surface markers (CD16, CD56, CD57) of peripheral blood lymphocytes were studied in patients with multiple myeloma and MGUS (monoclonal gammopathy of undetermined significance). A strong correlation (p less than 0.0001) was found between the numbers of cells positive for the different NK cell surface markers. The proportion of CD16+ cells correlated highly to the lytic capability (lytic units/10(6) cells) of K562 cells (p less than 0.0001). High NK activity and high numbers of cells with NK-related cell surface markers were found in patients with a low tumor burden compared to controls, whereas low values were seen in patients with an advanced disease. The results indicate that NK cells might be involved in the disease process in monoclonal gammopathies, perhaps by exerting a regulatory function on the proliferating B-cell clone.

Adult↗

Reappraisal of uterine sarcoma diagnosis in the Swedish Cancer Registry.

An investigation of over- and under-registration of uterine sarcomas in the Swedish Cancer Registry during the period 1958-1980 was carried out. A histopathologic review of a 10% sample (159 cases) revealed that 18% of the cases, the majority of which were benign leiomyomas, could not be reclassified as sarcomas. All 186 cases of uterine sarcoma treated at Radiumhemmet during the period 1958-1980 were found in the Cancer Registry, but only 90% as sarcomas. As a consequence of over- and under-registration of the sarcoma tumors, the estimated incidences will be affected. In this study, however, we could not find any time trend in the erroneous registration, which implies that comparisons in incidence over time would still be valid.

Diagnostic Errors↗

Estrogen and progesterone receptors in the human thymus.

Thymus tissue samples from 8 prepubertal children of both sexes were analyzed for estrogen and progesterone receptors. With the use of an enzyme immunoassay, estrogen receptors in both the cytosol and nuclear fraction were detected. The mean concentration (+/- SD) of receptors in the cytosol fraction was 2.1 +/- 0.9 and for the sum of receptors in both fractions 2.8 +/- 1.0 fmol/mg of protein. In addition low concentrations of progesterone receptors (mean value +/- SD = 0.9 +/- 0.3 fmol/mg of protein) were detected in all investigated samples. The presence of estrogen receptors in the nuclear fraction and of progesterone receptors suggests that the estrogen receptors may be active in mediating a physiological response and thus supports the view that the human thymus is a target organ for estrogens.

Child↗

When does external cephalic version succeed?

From 1984 to 1987, 300 pregnant women with fetal malpresentations underwent an attempt at external cephalic version (ECV) during the last trimester. A consecutive analysis of factors associated with successful version was performed during this period. The final version rate after one or more attempts was 58%, being lower in nulliparous (39%) than in parous women (80%). Multivariate analyses (logistic regression) identified only three significant variables out of 16 with independent power to explain successful version. The overall most important factor was parity (p less than 0.001), followed by fetal presentation (p less than 0.001) and amount of amniotic fluid (p = 0.019).

Breech Presentation↗

Malignant disease after radiation treatment of benign gynaecological disorders. A study of a cohort of metropathia patients.

One hundred and seven cases of malignant tumours occurred among 788 women irradiated 1912 to 1977 for metropathia. One hundred and seventy-three women out of 1,219 referred for the same diagnosis and not irradiated developed a malignant tumour. The tumours were diagnosed between 1958 and 1982. The relative risk of malignant tumours among the irradiated women was 1.22 and among the non-irradiated 1.09 compared to cancer registry data. A statistically non-significant increase of the relative risk was found in the irradiated patients for tumours of the rectum (1.58), colon (1.46), and the nervous system (1.67). A decreased overall relative risk was seen for cancer of the breast (0.92) after irradiation, but women treated at the age of 50 or more had an increased risk (2.08). The relative cancer risk of the heavily irradiated sites was not increased during the first 20 years after irradiation, but a statistically significant increase of the risk was seen after 30 years.

Brachytherapy↗

Plasma pharmacokinetics of Idarubicin and its 13-hydroxymetabolite after intravenous and oral administration under fasting and non-fasting conditions.

The plasma pharmacokinetics of Idarubicin and its 13-hydroxy-metabolite have been studied in 10 patients with solid tumours after intravenous and oral administration under fasting and non-fasting conditions in a randomized cross-over design. The plasma concentration time curves of Idarubicin after intravenous administration could be described by the open two or three compartment models. No pharmacokinetic modelling of Idarubicin was possible after oral administration. After oral administration of Idarubicin, the amount of intact drug was higher under non-fasting conditions. The extensive and long-lasting appearance of Idarubicinol suggests that this cytotoxic metabolite is of major clinical importance in i.v. and oral therapy with Idarubicin. The pharmacokinetics of Idarubicinol was not affected by food intake.

Administration, Oral↗

Prognostic factors in uterine leiomyosarcoma. A clinical and histopathological study of 143 cases. The Radiumhemmet series 1936-1981.

One hundred and forty-three patients with uterine leiomyosarcomas treated at Radiumhemmet from 1936 through 1981 were reviewed. Clinical and histopathological findings were analysed by bivariate and multivariate analyses to assign prognostic factors. Mitotic count, menopausal status and stage showed to be significant predictors of survival. The series was divided into two periods of time and a significantly higher survival rate in the second period was noted for patients with stage I disease. Thirty-seven patients with tumors showing less than 10 mitotic figures per 10 high power fields had a 5-year survival rate of 65% compared with 17% for 106 patients with 10 or more mitotic figures per 10 high power field. No significant predictor of a bad outcome for these low mitotic count tumors was found.

Female↗

Effects of the new undergraduate dental curriculum of 1979.

A new curriculum for dental education was introduced in Sweden in 1979. Among other things the basic training was cut down from 10 to 9 semesters and a preregistration year in the Public Dental service was added. In this study two cohorts of dentists, one having studied under the old and one under the new curriculum, having 1 to 3 years practical experience of the dental profession, were asked to evaluate their undergraduate education as seen from a practising dentist's point of view. The results showed that the dentists trained under the new curriculum regarded their theoretical knowledge, clinical skills, and the relevance of their training generally higher than those trained under the old curriculum. However, the correlations between the old and the new curriculum with respect to the rankings of the individual subjects were high, indicating that no radical changes had occurred in the preference orders of the subjects. The self-estimated importance of different subjects for the dental profession may reflect the dentists' present working situation, e.g. the Public Dental Service or private practice.

Adult↗

A role of herpes virus serology for the development of acute graft-versus-host disease. Leukaemia Working Party of the European Group for Bone Marrow Transplantation.

Pretransplant herpes virus serology and acute graft-versus-host disease (GVHD) were studied in 379 leukaemic bone marrow transplant (BMT) recipients and their HLA-identical sibling donors. In logistic multivariate regression analysis pretransplant seropositivity to three or more different herpes viruses among the recipients was the only significant factor associated with grade II-IV acute GVHD (p = 0.03). If this factor was excluded, older donor age (p less than 0.001), absence of T cell depletion (p less than 0.001), pharmacological immunosuppression by monotherapy of methotrexate or cyclosporin versus a combination therapy of both (p = 0.002), and seropositivity to three or more herpes viruses among the donors (p = 0.03) prior to BMT, were also significantly associated with acute GVHD. The data indicate that latent herpes viruses in the host may act as minor histocompatibility antigens or by other means to trigger acute GVHD.

Adolescent↗