Biomedical subjects

B Nilsson

Publications and source records attributed to B Nilsson.

At least 163 records · Page 9Linked to original sources

PubMed1996

Tubing loops as a model for cardiopulmonary bypass circuits: both the biomaterial and the blood-gas phase interfaces induce complement activation in an in vitro model.

We describe here a model for the study of blood/surface and blood/air interaction as encountered in cardiopulmonary bypass (CPB) circuits. Polyethylene tubing was filled with serum or blood and closed end to end into loops whereby the volume of the remaining air bubble was inversely varied with respect to that of the fluid. The loops were rotated vertically in a water bath at 37 degrees C. The profiles of C3a, iC3, and TCC generation were similar to those observed at surgery, involving CPB. Soluble heparin and heparan sulfate inhibited both C3a and TCC formation, but surface-conjugated heparin had only a minor effect. Binding of C3 and/or C3 fragments to the heparin surface was much reduced compared to the amine matrix to which heparin was linked, but compared with the polyethylene surface the effect was less pronounced. These data suggest that, in addition to the biomaterial surface, the blood-gas interface seems to play an important role in the activation of complement and that this activation is inhibitable by high concentrations of soluble glucose aminoglycans.

Biocompatible Materials↗

PubMed1996

Prognostic significance of c-erb-B2 amplification in fine-needle biopsies of breast cancer patients not operated at diagnosis.

Prognostication of breast cancer patients, not operated at diagnosis, poses a clinically difficult problem. To use gene amplification we examined cytological samples and determined c-erb-B2 gene copy number with semi-quantitative PCR. Control experiments showed the same gene-copy number in aliquots that were either air-dried (and MGG-stained), fixed in methanol (and air-dried), or snap-frozen in liquid nitrogen. Therefore we examined the prognostic value of c-erb-B2 amplification in 95 breast cancer patients that had not been operated at diagnosis (up to 12 years previously). Tumor cells were obtained from routine archival cytological smears. 15 patients (16%) had developed amplification. Univariate and multivariate analysis showed that c-erb-B2 amplification is a significant prognostic factor (p < 0.0001). Hence routine cytological MGG smears can be used for prognostic determination.

Adult↗

PubMed1996

Improved survival of patients with papillary thyroid cancer after surgical microdissection.

A total of 195 patients had surgery for papillary thyroid cancer. The mean age at operation was 50 years. A microdissection technique was used for total thyroidectomy and lymph node clearance. Postoperative radioiodine tests showed no uptake or an uptake close to the background activity in 77% of the examined patients. By counting the lymph nodes removed at surgery we were able to check on the quality of the lymph node dissection. Men had a higher incidence (70%) of lymph node metastases than women (45%). Only 4% of the patients had radioiodine ablation of the thyroid remnant. The median follow-up time was 13 years. None of the patients below 45 years of age at surgery died of thyroid cancer. In the older age group eight patients died of thyroid cancer at a mean age of 75 years. Five of those who died of a thyroid carcinoma had distant metastases at diagnosis. Among patients with resectable disease, three (1.6%) died of thyroid cancer, all of whom had lived for more than 17 years after surgery. Hence longer follow-up is needed before we know the final mortality in our series. The results suggest that surgical technique and strategy can positively influence the survival of patients with papillary thyroid cancer.

Adolescent↗

PubMed1996

Tumor-specific deposition of immunoglobulin G and complement in papillary thyroid carcinoma.

Despite its predilection for multifocal growth and regional metastasis, papillary thyroid carcinoma (PTC) is a clinically indolent malignancy with an exceptionally favorable long-term prognosis. Together with the often striking inflammatory reaction present in PTC, its quiescent behavior has been suggested to reflect the activation of a tumor-induced immune response. To examine this possibility, we have studied the deposition of immunoglobulins and complement in PTC tissue. Samples from 70 cases of neoplastic and autoimmune thyroid diseases, including PTC (n = 41), follicular, anaplastic, and medullary carcinomas (n = 12), follicular adenoma (n = 6), Graves' disease (n = 8), and Hashimoto's thyroiditis (n = 3) were analyzed immunohistochemically. Cellular deposits of immunoglobulin G (IgG), particularly subclasses IgG1 and IgG4, and complement factors C3d, C4d, and C5 were shown in up to 80% of the PTC cases, whereas the other thyroid diseases studied showed little or no cellular deposition. Nonneoplastic tissue of PTC-containing thyroid glands (n = 22) lacked staining for IgG in 50% of the cases, and 82% were devoid of complement. The results suggest a tumor-specific immune response in PTC with activation of the classical complement cascade.

Adolescent↗

PubMed1996

Affinity-assisted in vivo folding of a secreted human peptide hormone in Escherichia coli.

We show that coexpression of a specific binding protein in Escherichia coli can significantly improve the relative yields of correctly folded human insulin-like growth factor I (IGF-I). A glutathione redox buffer was used during growth to allow formation and breakage of disulfide bonds in the periplasm of the bacterial host. Both the binding protein and the peptide hormone were produced as affinity fusions, which allowed purification of the in vivo formed heterodimer by alternative affinity purification methods. The use of affinity-assisted in vivo folding has general implications for expression, folding, and purification of recombinant proteins.

Affinity Labels↗

PubMed1996

VIP-antiserum and indomethacin inhibit calcium and bicarbonate secretion by the inflamed feline gallbladder mucosa.

Ionized calcium (Ca2+) and bicarbonate (HCO(3)-) are important ions for gallstone formation. In the present study the effect of indomethacin and vasoactive intestinal peptide-antiserum (VIP-antiserum) on the Ca2+, HCO(3)- and fluid secretion in the inflamed gallbladder were tested in a validated experimental model in cats. The animals were studied in acute experiments 6 weeks after cystic duct ligation and gallstone implantation. During basal conditions there was a continuous secretion of Ca2+, HCO(3)- and fluid into the lumen of the inflamed gallbladder. Indomethacin and VIP-antiserum inhibited the Ca2+, HCO(3)- and fluid secretion across the inflamed gallbladder mucosa. Intraluminal amiloride inhibited the absorption of Ca2+, HCO(3)- and fluid after indomethacin infusion. An impaired absorption of Ca2+, HCO(3)- and fluid in the inflamed gallbladder is probably important for the solubility of calcium salts in the early stages of inflammation in the gallbladder mucosa.

Animals↗

PubMed1996

Blood clonal B-cell excess in patients with monoclonal gammopathy of undetermined significance (MGUS): association with malignant transformation.

Fifty-seven patients with monoclonal gammopathy of undetermined significance (MGUS) were analysed for the presence of blood clonal B-cell excess (CBE), defined as a lymphocyte surface membrane kappa/lambda light chain ratio outside the normal range (> 3.5 in kappa-type MGUS and < 0.9 in lambda-type MGUS). 15 patients (26%) had a CBE. The patients were followed for a median time of 8.4 years (range 0.5-20.2). Eight of the 15 CBE+ MGUS patients (53%) developed a B-cell malignancy as compared to 7/42 patients (17%) in the CBE group and the difference in event-free (malignancy-free) observation time was statistically significant (P = 0.01). Cox's regression analysis showed that the presence of CBE was the most powerful predictor of progression to a malignant disease. Two patients with a normal kappa/lambda ratio at first test were analysed repeatedly during follow-up. Subsequently, a CBE appeared which gradually increased in size preceding the clinical diagnosis of a malignant disease.

Adult↗

PubMed1996

Role of nitric oxide in induction of inflammatory fluid secretion by the mucosa of the feline gallbladder.

BACKGROUND & AIMS: Nitric oxide is synthesized from L-arginine and is metabolized to nitrate and nitrite. This study evaluates the effects of a pharmacological blockade of NO synthesis on fluid transport by the inflamed gallbladder mucosa. METHODS: Experiments were performed in cats with cholecystitis and in control animals. NO synthase activity was measured in gallbladder tissue; the enzyme was characterized by immunoblotting techniques and localized by immunofluorescence. Fluid transport and release of nitrate and nitrite by the gallbladder mucosa and bile and bile salt secretion from the liver were registered simultaneously in vivo. RESULTS: Fluid secretion in inflamed gallbladders was reversed to a net absorption in response to the NO synthase blockers N omega-nitro-L-arginine and aminoguanidine, and formation of nitrate was reduced. The effects were reversed by L-arginine. Increased levels of inducible NO synthase in inflamed gallbladders were shown by immunoblotting, by immunofluorescence (mainly in macrophages), and by Ca(2+)-independent [3H]citrulline formation from [3H]arginine. The NO synthase blockers had no effect on gallbladder fluid transport in normal gallbladders. CONCLUSIONS: Increased levels of inducible NO synthase activity are shown in inflamed gallbladders, and a pharmacological blockade of this enzyme blocks fluid secretion and decreases nitrate release from the mucosa.

Analysis of Variance↗

PubMed1996

Wall effects in plane-parallel ionization chambers.

All dosimetry protocols recommend the use of plane-parallel chambers for dose determination in electron beams with energies below 10-15 MeV. The protocols have assumed chamber perturbation effects to be negligible. The new AAPM Protocol (TG39) includes a cavity replacement factor prepl that differs from unity for some chambers, but assumes that the wall perturbation factor, pwall, may be taken as unity. In this paper the perturbation of the wall has been determined, using a large plane-parallel ionization chamber with exchangeable front and back walls. The results show that in many commercial chambers there is an energy dependent pwall factor, mainly due to differences in backscatter from the often thick chamber body as compared to the phantom material. Backscatter in common phantom and chamber materials may differ by as much as 2% at low electron energies (Plastic Water as compared to polystyrene). The front walls are often thin, resulting in negligible perturbation, but the 0.5 mm front wall of graphite in the NACP chamber was found to increase the response by 0.7% in a PMMA phantom. The experimental results have been compared with EGS4 Monte Carlo calculations using the DOSRZ code. There is an agreement within statistical and experimental uncertainties (0.5%) indicating that it is possible to use Monte Carlo calculations to calculate perturbation factors with good accuracy.

Graphite↗

PubMed1996

Prognostic value of serum analyses of S-100 beta protein in malignant melanoma.

S-100 protein was first described in the central nervous system but is also present in malignant melanoma cells. Immunohistochemical detection of S-100 is widely used in the histopathological diagnosis of malignant melanoma. In the present study serum levels of S-100 beta protein were measured in 643 patients with cutaneous malignant melanoma. An immunoradiometric assay with three monoclonal antibodies against bovine S-100 protein beta subunit was used. At the time of blood sampling 553 patients were in clinical stage I, 24 in clinical stage II and 66 in clinical stage III. The overall survival rate was strongly associated with serum levels of S-100 protein. The observed/ expected death ratio was markedly increased with increasing levels of S-100 beta (P < 0.001). A fivefold increase in relative hazard was indicated by a value of S-100 beta exceeding 0.6 microgram/l (P < 0.001) and when this cut-off level was used S-100 beta had additional prognostic value independent of clinical stage (P < 0.001). Our data strongly suggest that S-100 beta in serum is an independent prognostic marker that may be useful in identifying high-risk cases and monitoring response to therapy in patients with malignant melanoma.

Adolescent↗

PubMed1996

Stepwise prediction of dental caries in children up to 3.5 years of age.

The present study is a part of a prospective, longitudinal investigation of caries development in children (n = 692) living in the southern suburbs of Stockholm. The aim was to evaluate, longitudinally, the caries-predictive ability of variables describing social and immigrant background, dietary habits, microbial and oral hygiene factors, and fluoride exposure in children at 1 and 2.5 years of age with respect to caries development before the age of 3.5. The predictors for caries development in children before 2.5 years of age were mutans streptococci (p < 0.01), immigrant background (p < 0.01), and consumption of candy (p < 0.01). The predictors for developing manifest caries between 2.5 and 3.5 years of age were mutans streptococci (p < 0.001), mother's education (p < 0.001), immigrant background (p < 0.01), and consumption of candy (p < 0.05) and sugar-containing beverages (p < 0.05). The caries incidence at 2.5 years of age as well as the caries increment between 2.5 and 3.5 years of age were significantly higher in children with immigrant background compared to non-immigrants. This study indicates that the possibility of identifying children at risk for caries development increases longitudinally from 1 to 3.5 years of age and there was a synergistic effect between age and each predictor.

Age Factors↗

PubMed1996

Primary culture of human thyrocytes in Transwell bicameral chamber: thyrotropin promotes polarization and epithelial barrier function.

Epithelial properties of thyrocytes are difficult to maintain in conventional cell culture systems. We used bicameral chambers (Transwell) in attempts to establish a functional epithelium of thyrocytes of human origin. Thyroid follicle segments were isolated by collagenase digestion of paradenomatous tissue obtained at surgery for follicular adenoma and of tissue from glands with Graves' disease. After careful separation from connective tissue and single cells by centrifugation, the follicles were plated at high density on the collagen-coated filter of the chambers and cultured in Eagle's essential medium (EMEM) containing 10% fetal calf serum (FCS) or Coon's modified Hams medium enriched with five or six factors (5H, 6H); the latter media contained 5% FCS without (5H) or with (6H) thyrotropin (TSH). The follicles were converted into a confluent cell layer, which had similar DNA content irrespective of type of medium, after 4-6 days. Cells grown in EMEM or 5H established a transepithelial electrical resistance (R) of 200-500 omega.cm2 and was impermeable to [3H]inulin, indicating the formation of epithelial junctions. Addition of 6H to confluent cells initially cultured in EMEM or 5H caused a further increase of R, maximally to 1500 omega.cm2, along with a rise of the transepithelial potential difference; 6H promoted the monolayer formation of cells, increased the number of apical microvilli and reinforced the junctional distribution of actin, cadherin and ZO-1; 6H also enhanced the polarized secretion of [3H]leucine-labeled thyroglobulin into the apical medium. Cells from Graves' thyroid tissue established an epithelium on the filter with similar characteristics to that of normal thyrocytes; some platings contained in addition large numbers of HLA-DR positive cells with a dendritic shape. HLA-DR expression was generally absent in EMEM-or 5H-grown thyrocytes, but appeared in limited areas of the cell layer after 6H and was expressed by all epithelial cells after interferon-gamma stimulation for 48 h. We conclude that human thyrocytes form a tight and polarized epithelium when cultured on permeable filters. The polarized structure and function of the cells are positively regulated by TSH. The culture system may be useful in studies addressing the role of the epithelial phenotype (cell polarity and tight barrier) in normal thyroid function as well as in pathological processes in the thyroid, such as autoimmunity, cell transformation and tumor progression.

Cell Polarity↗

PubMed1996

Effect of palatal plate therapy in children with Down syndrome. A 1-year study.

The effect of palatal plate therapy on oral dysfunction in children with Down syndrome was studied during a 1-year period. Twenty-nine subjects with a mean age of 24 months were randomized to a test group or to a control group. The variables concerning orofacial muscle function--that is, "closed mouth', "tip of the tongue visible', "open mouth', "inactive protrusion of the tongue', and "active protrusion of the tongue'--were monitored by video recordings. After 12 months of therapy the mean duration of the factor "closed mouth' was significantly longer (p < 0.001) and "inactive protrusion of the tongue' significantly shorter (p < 0.001) in the test group than in the control group. The results indicate that in children with Down syndrome, palatal plate therapy may be a valuable complement to a training program for improving orofacial muscle function.

Child, Preschool↗

PubMed1996

Biological malignancy grading in early-stage ovarian carcinoma.

The usefulness of adjuvant therapy in early ovarian cancer is a matter of controversy and there is a need for predictive methods to distinguish between low and high risk patients. Specimens from 95 early-stage ovarian cancer patients have been analysed for conventional clinical variables as well as for the biological markers--DNA content, MIB-1, p53, WAF-1--and correlated to survival. Prognostic significance achieved in univariate analysis could be improved by using a score based on several biological markers. Using a score based on DNA content, MIB-1, p53 and WAF-1, a significant predictor could be achieved with the aim of determining the postsurgical therapy. By using this tool, it is hoped that adjuvant therapy can be avoided for one-third of the patients with early-stage ovarian cancer.

Adult↗

PubMed1996

Secondary antibodies as tools to improve tumor to non tumor ratio at radioimmunolocalisation and radioimmunotherapy.

One way of selectively improving the efficiency of radioimmunolocalization and radioimmunotherapy is to eliminate redundant, circulating, non-targeting radiolabeled antibodies after saturation of the target sites. Secondary antibodies of different types have been proposed as clearing agents for such purposes. The conceptually different approaches of the 'secondary antibody' strategy including its advantages and limitations are discussed. This mini-review also presents a model describing the kinetics of the components (the antigen, the primary and secondary antibodies) and approaches required to improve the efficacy of both radioimmunolocalization and radioimmunotherapy.

Animals↗

PubMed1996

Sunbed use in relation to phenotype, erythema, sunscreen use and skin diseases. A questionnaire survey among Swedish adolescents.

Sunbed use was studied in relation to phenotype, erythema, sunscreen use and skin disease. The study population comprised 14-19 year-old Stockholm adolescents in 60 randomly selected classes, with 1252 students providing information. More than half (57%) reported sunbed use > or = 4 times during the previous year. Skin type III dominated (64%). Excessive exposure (> or = 10 times/year) was not correlated to skin type. Sunscreens were most commonly used by sunbed users. Of all sunbed users, 44% reported erythema. Adolescents with acne/seborrhoca, eczema or psoriasis used sunbeds more than others without skin diseases. The proportion with sunbed erythema (44%) indicates an unrecognized susceptibility to artificial ultraviolet radiation (UVR) among adolescents. The association between high exposure to UVR and sunscreen use stresses the importance of sunscreens being used as supplementary protection, not as a tool for tanning.

Adolescent↗

PubMed1995

Use of anticytokeratin monoclonal anti-idiotypic antibodies to improve tumor:nontumor ratio in experimental radioimmunolocalization.

A syngeneic, high-affinity, anti-idiotypic monoclonal antibody (MAb; alpha TS1) raised against an anticytokeratin monoclonal antibody (TS1) was evaluated as a second antibody to promote the rapid clearance of radiolabeled TS1 from the blood during experimental radioimmunolocalization. By using a novel biosensor technology (BIAcore), association rate dissociation rate, and affinity constants between the idiotype and the anti-idiotype could be determined. The in vivo results in nude mice carrying HeLa Hep 2 tumors demonstrate the possibility of selectively regulating the amount of the idiotypic 125I-labeled circulating MAb by in vivo injection of this high-affinity, anti-idiotypic antibody. Injection of the anti-idiotype in a molar ratio of 0.75 to the idiotype cleared the blood pool from circulating radiolabeled idiotype within 24 h, with a concomitant rapid excretion of 125I in urine. The total amount of remaining radioactivity in the animals decreased to 15-20% during these 24 h, with the tumors still retaining 60-65% of their initial radioactivity. This approach, using syngeneic primary and secondary MAbs with minimized immunogenicity, significantly improves the tumor:nontumor ratio, thus improving efficiency in experimental radioimmunolocalization and radioimmunotherapy, leaving the endogenous antibody repertoire of the host unaffected.

Animals↗

PubMed1995

Phosphorylation of complement component C3 and C3 fragments by a human platelet protein kinase. Inhibition of factor I-mediated cleavage of C3b.

Phosphorylation of C3 in vitro has been shown previously to lead to significantly altered function of the protein. Platelets are known to contain and release considerable amounts of protein kinases and ATP, which are prerequisites for protein phosphorylation. The aim of the present study was to investigate whether C3 is phosphorylated extracellularly by human platelets. Platelet-rich plasma was stimulated by human aggregated gamma-globulin or ADP. The remaining cells were removed by centrifugation, and the plasma was incubated with [gamma-32P]ATP. After precipitation with Sepharose-bound Abs to C3c followed by SDS-PAGE, it was shown that C3 was phosphorylated in the alpha-chain by a protein kinase dependent on Mn2+, Ca2+, or Mg2+ ions. The supernatant from washed, activated platelets was incubated with purified C3 or soluble or activated thiol Sepharose-bound C3b, together with [gamma-32P]ATP. Phosphorylation was seen in the alpha-chain of C3, and to the same extent in the alpha'-chain of both C3b preparations. The analysis of acid hydrolysate demonstrated that C3 contained 32P-labeled Thr and 32P-labeled Ser. After extensive proteolysis with trypsin, the major phosphorylation site was located to a peptide of 3 to 4 kDa that was bound to the activated thiol Sepharose via the free sulphydryl group in the C3d fragment. Incubation of phosphorylated C3b with factors I and H showed that phosphorylation inhibited the cleavage of the alpha'-chain of C3b. The results in this study suggest that phosphorylation is a regulator of C3 during platelet activation induced, for example, by immune complexes.

Binding Sites↗