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Biomedical subjects

B Nilsson

Publications and source records attributed to B Nilsson.

At least 307 records · Page 17Linked to original sources
PubMed1991

Prognostic factors in invasive squamous cell carcinoma of the vulva.

Histological malignancy grading and its correlation to prognosis were retrospectively investigated in 303 cases of squamous cell carcinoma of the vulva. A scoring system based on several variables is suggested. The scores and the individual histological variables were tested along with clinical factors with a view to predicting survival. Various histological variables including mode of invasion, depth of invasion and nuclear polymorphism, as well as the sum of the scores were good predictors of survival. The study revealed a significantly better survival rate in stage III if no metastases were suspected. An age factor was also found showing that cancer of the vulva has a worse prognosis in older women.

Adult↗
PubMed1991

Digoxin-verapamil interaction: reduction of biliary but not renal digoxin clearance in humans.

The interaction between digoxin and verapamil was studied in six patients (mean age +/- SD, 61 +/- 5 years) with chronic atrial fibrillation. The effects of adding verapamil (240 mg/day) on steady-state plasma concentrations and renal and biliary clearances of digoxin were studied in a crossover manner. The biliary clearance of digoxin was determined by a duodenal perfusion technique. Verapamil induced a 44% increase in steady-state plasma concentrations of digoxin, from 0.80 +/- 0.24 to 1.15 +/- 0.40 nmol/L (p less than 0.01). The biliary clearance of digoxin decreased by 43%, from 187 +/- 89 to 101 +/- 55 ml/min (p less than 0.05), in the presence of verapamil, whereas the renal clearance was unaffected (153 +/- 31 versus 173 +/- 51 ml/min; difference not significant). Our results indicate that the main inhibitory effect of verapamil on digoxin elimination is on the biliary route.

Bile↗
PubMed1991

Engineering proteins to enhance their partition coefficients in aqueous two-phase systems.

We describe a novel method to partition recombinant proteins into the polymer-rich top phase in poly(ethylene glycol) (PEG)4000/potassium phosphate aqueous two-phase systems. The concept is based on fusion of a gene fragment encoding a short peptide sequence to the product gene of interest thereby changing the partitioning properties of the expressed product protein as a fusion to the peptide. The model protein in this study, ZZ, is a two domain molecule based on staphylococcal protein A (SPA) which distributes evenly in PEG/salt systems. A tetrapeptide sequence, AlaTrpTrpPro (designated the partitioning peptide), was designed by molecular modeling techniques to include exposed tryptophan residues and to have a coding DNA sequence which is possible to polymerize in an obligate head-to-tail fashion at the DNA level. Gene fragments encoding one and three partitioning peptides, respectively, were fused to the 3' end of the ZZ gene and the fusion proteins were produced intracellularly in Escherichia coli. The partition coefficients of ZZ proteins containing zero, one and three fused partitioning peptides were determined in three PEG 4000/potassium phosphate aqueous two-phase systems of different compositions. In all three phase systems, there were dramatic effects on the partition coefficient by the fused partitioning peptides. In the phase system with the largest effects, the partition coefficient was enhanced from 1.6 to 11.6 by fusing one tetrapeptide sequence to the 147 amino acid model ZZ protein. By the fusion of three partitioning peptides, the coefficient was increased to 96.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acid Sequence↗
PubMed1991

A new assay for transglutaminase.

A new solid-phase micro assay for transglutaminase has been developed. Casein bound to microtitre plates and biotin-labelled casein were used as substrates in a transglutaminase-dependent cross-linking reaction. The resulting immobilized biotin was visualized by addition of avidin-labelled alkaline phosphatase followed by p-nitrophenyl phosphate. The colour development was monitored at 405 nm. Tissue transglutaminase was used as test enzyme. The method was also applied to normal and Factor XIII-deficient plasma.

Alkaline Phosphatase↗
PubMed1991

Induction of anti-idiotypic (ab2) and anti-anti-idiotypic (ab3) antibodies in patients treated with the mouse monoclonal antibody 17-1A (ab1). Relation to the clinical outcome--an important antitumoral effector function?

Forty-three patients with metastatic colorectal carcinoma (CRC) were treated with the unconjugated mouse monoclonal antibody (MAb) 17-1A (ab1) only. The presence of antiidiotypic antibodies (ab2) and anti-antiidiotypic antibodies (ab3) were analyzed using an ELISA technique and a mixed hemadsorption assay respectively. Ninety-five percent (41/43) of the patients developed ab2 both of the IgM and the IgG classes. Forty-seven percent (20/43) of the patients had detectable ab3 after therapy, two of them also before administration of MAb 17-1A. Binding in vitro of ab3 (ab1) to CRC cells could be specifically inhibited by ab1. Ab3 bound to human monoclonal antiidiotypic antibodies and to a goat antiidiotypic antibody (ab2). Both these ab2 were directed against MAb 17-1A (ab1). There was a strong correlation between the presence of ab3 and the clinical outcome. Ab3+ patients survived significantly longer than those who did not develop ab3 antibodies, 80 weeks vs 38 weeks (p less than 0.001). A statistically significant correlation was found between the presence of ab3 and the anti-tumor response (CR + PR + MR + SD) (p = 0.01). Thus, induction of an antiidiotypic cascade seems to be an important antitumor effector function of MAb in the treatment of cancer patients.

Antibodies, Anti-Idiotypic↗
PubMed1991

Intracellular expression of BPTI fusion proteins and single column cleavage/affinity purification by chymotrypsin.

The novel and efficient expression system described here produces formerly poorly expressed, proteolytically unstable mutants of bovine pancreatic trypsin inhibitor (BPTI). A new, single column method for the cleavage of a recombinant fusion to BPTI and affinity purification of the BPTI moiety by immobilized chymotrypsin is an integral part of the system. Wild-type and mutant BPTI molecules are expressed in Escherichia coli as fusion proteins forming intracellular inclusion bodies. Transcription initiation is under the control of the E. coli trp promoter. The expressed protein is tripartite fusion comprising (i) a portion of the TrpLE leader peptide, (ii) a synthetic IgG binding domain derived from protein A and (iii) the BPTI variant. Solubilization of the inclusion bodies and refolding of the fusion proteins in a thiol-disulfide shuffling system yields correctly folded inhibitor molecules. In the single column purification and cleavage procedure, immobilized chymotrypsin cleaves the refolded fusion protein and releases affinity purified active BPTI mutants with correct N-termini. Mutant BPTI molecules which do not fold into active inhibitors are also stably expressed in inclusion bodies but cannot be purified by this method. Unlike previously described secretion systems for the production of BPTI, expression levels in this system appear to be independent of both the mutation in the BPTI gene and the activity of the expressed protein. Mutants poorly expressed in secretion systems can now be produced in sufficient quantities for protein folding studies and structural analysis using X-ray crystallography and NMR spectroscopy.

Amino Acid Sequence↗
PubMed1991

An improved method to study complement receptor-mediated function of the fixed macrophage system in vivo.

A method to coat unsensitized erythrocytes with fragments of C3 and C4 using autologous serum, in order to study complement receptor-dependent function of the fixed macrophage system, is presented. After incubation with serum under optimal conditions, at least 90% of the cells had C3b/iC3b deposited on the surface, with an average of 20 x 10(3) molecules per cell. Elimination of the coated cells by the fixed macrophage system was studied in 12 normal subjects. With a dose of 4.5 x 10(8) red cells injected, 75% of the cells were eliminated with a half-life of approximately 2.4 +/- 0.3 min (n = 7). In subjects receiving ten times more cells, there was a rapid decrease in the amount of C3-coated cells, reaching a nadir with 85% remaining for 4-6 min, after which there was a gradual release of cells for another 20 min (n = 5). In absolute numbers, 3 x 10(8) of labeled cells were eliminated regardless of the dose injected. The coating procedure presented here is simple, does not introduce heterologous blood components and makes it possible to control the amount and the degree of fragmentation of the C3 and C4 deposited on the erythrocyte surface.

Adult↗
PubMed1991

Short-term radiotherapy as palliative treatment in patients with transitional cell bladder cancer.

We report the results and complications of treatment with palliative, short-term radiotherapy in 162 elderly or disabled patients. Improvement in tumour-associated symptoms was noted in 75 of these patients and 72 survived for more than a year. Those who responded to radiotherapy had a 5-year cancer-free survival rate of 58% compared with 4% in patients who did not respond to treatment. Survival was also affected by stage and indications for radiotherapy. In 85 patients without severe symptoms, where the tumour was judged curable but the patient was unsuitable for a full course of radiotherapy, the 5-year cancer-free survival rate was 21%, which is in accordance with what can be achieved with full-course radiotherapy; 42% had various minor acute side effects. The 5-year late complication rate was 7%.

Aged↗
PubMed1991

Psychiatric symptoms in alcoholics attending outpatient treatment.

The importance of psychiatric symptomatology for the treatment course of alcoholics was analyzed in a long-term outpatient treatment study. Seventy-two patients, 60 men and 12 women, were personally interviewed during treatment and after 3 years. Before treatment psychiatric symptoms were rated according to the Comprehensive Psychopathological Rating Scale (CPRS). Women had significantly higher scores than men. Men with many symptoms and women had more psychological benefits from drinking and a more impaired personality structure than men with few symptoms. Men with many symptoms also had a lower level of social functioning. The severity of abuse did not differ between the three groups. Men with many symptoms had a less favorable outcome between 25 and 36 months after start of treatment than men with few symptoms and women. Among men who completed treatment, those with many symptoms showed a less successful course after 6 months and during the 3rd year after start of treatment, while differences after 3 months and during later stages of treatment were less pronounced. It is suggested that before start of treatment a psychiatric evaluation should be performed including psychiatric diagnosis, personality analysis, and an assessment of psychological benefits from drinking.

Adult↗
PubMed1991

Acute leukemia in professional drivers exposed to gasoline and diesel.

The environmental exposure to the petroleum products gasoline, diesel, and their motor exhausts was studied in a case-control interview of 125 patients with acute leukemia and 1 matched control per patient. Odds ratios were calculated by comparing discordant matched patient-control pairs. An excess risk for developing acute leukemia was found for the professional drivers, and odds ratio was determined to be 3.0 (95% CI: 1.1-9.2/p less than or equal to 0.02). For those who were exposed for more than 5 years in their life-time, or more than 1 yr during the 5-20 yr period prior to diagnosis, the odds ratio was 5.0 (p less than 0.05). This finding remains after consideration is given to exposures to organic solvents, smoking and therapeutic x-ray treatment. No excess risk was observed for persons professionally exposed to motor oil and machine oil without exposure to fuels and exhausts. No preferential type of acute leukemia was found to be associated with exposure to fuels and their exhausts. The results indicate an etiological relationship between the development of acute leukemia and exposure to petroleum products as fuels and exhaust.

Acute Disease↗
PubMed1991

Fc receptor function and circulating immune complexes in gluten sensitive enteropathy--possible significance of serum IgA.

The capacity to clear IgG containing immune complexes from the circulation was studied in patients with coeliac disease (n = 13), dermatitis herpetiformis (n = 8), and coeliac disease with concomitant serum IgA deficiency (n = 4). A small group of patients with active ulcerative colitis (n = 4) was included as a bowel disease control group. Clearance was estimated by measuring the disappearance rate of a bolus dose of intravenously injected IgG coated autologous erythrocytes. The mean T1/2 of clearance was prolonged in both coeliac disease (86 (24) minutes) and dermatitis herpetiformis (111 (35) minutes), compared with healthy subjects (20 (5) minutes) and coeliac patients with concomitant serum IgA deficiency (T1/2 = 17 (6) minutes). Patients with ulcerative colitis had a prolonged clearance, with a T1/2 of 195 (63) minutes. Values of circulating immune complexes were measured by four assays; C1q binding and C3, IgG, and IgA containing immune complexes. C1q binding immune complexes were detected only in IgA deficient gluten sensitive enteropathy. Patients with coeliac disease and dermatitis herpetiformis had higher values of C3, IgG, and IgA containing immune complexes than control subjects and serum IgA deficient patients with coeliac disease. The clearance rate was inversely correlated to the amount of immune complexes for the subgroups of gluten sensitive enteropathy.

Adult↗
PubMed1991

Proper and improper folding of proteins in the cellular environment.

Protein folding in the cellular environment involves an interplay between the intrinsic biophysical properties of a protein, in both its folded and unfolded states, and various accessory proteins that aid the process. Factors such as peptidyl prolyl isomerase, protein disulfide isomerase, thioredoxin, and SecB may interact with the unfolded forms of specific classes of proteins, while members of the hsp70/DnaK and hsp60/GroEL molecular chaperone families may play a more general role in folding. Secretion, proteolysis, and aggregation are other in vivo processes that depend greatly on the folding behavior of a given protein. Intrinsic folding rates, or even translation rates, of nascent proteins may be optimized by natural selection to ensure smooth coordination with all the cellular components required for a successful folding reaction.

Bacterial Proteins↗
PubMed1991

Clinical signs and laboratory markers in predicting progression to AIDS in HIV-1 infected patients.

In a prospective longitudinal study 89 men with HIV-1 infection were observed for a mean time of 51 months with regard to clinical signs and laboratory findings predictive of progression to AIDS/opportunistic infection (OI). In a bivariate regression analysis the clinical signs showing a significant relation to AIDS development were: dermatitis of the face, yellow toe nail changes, hairly leukoplakia and oral candidiasis. The laboratory findings significantly associated with progression to AIDS were: decrease of the relative and absolute number of CD4 lymphocytes, decrease of the CD4/CD8 ratio, HIV p24 antigenaemia, lack of anti-HIV p24, elevated erythrocyte sedimentation rate, anaemia and elevated serum-beta-2-microglobulin. The relative number (%) of CD4 cells was found superior to the absolute number and the CD4/CD8 ratio. In a multivariate regression analysis decrease of CD4 lymphocytes and lack of anti-HIV p24 were independently associated with subsequent AIDS/OI development.

Acquired Immunodeficiency Syndrome↗
PubMed1991

Cytological diagnosis from fine needle aspiration biopsy of the liver.

One hundred and six fine needle aspiration biopsies (FNAB) of the liver were performed on 99 patients to rule out hepatic malignancy. Biopsies were performed with CT guidance (60), ultrasonography (40), fluoroscopy (3), by direct palpation (2) and intra-operatively (1). The smears and cell blocks were reviewed and the cytologic diagnoses were made after clinicopathologic correlation. Eight cases were excluded (six non-diagnostic and two mislaid). Fifty-two were positive, 2 suspicious and 44 negative for malignancy. There were no false positive results. The sensitivity for malignancy was 84.4%, the specificity was 100% and the predictive value of positive results was 100%. The false negative rate was ten out of 44 cases (22.7%). Of the malignant aspirates, there were 27 hepatocellular carcinomas, 21 metastases and four carcinomas of unknown histogenesis. Common benign lesions included abscesses, cysts, cirrhosis and steatosis. For FNAB to be an effective diagnostic procedure, adequate representative sampling, cell block preparation for appraisal of histological architecture and experience in cytomorphologic interpretation are necessary to increase yield and enhance precision of diagnosis.

Adult↗
PubMed1991

Effect of short-term indomethacin treatment on the clinical course of acute obstructive cholecystitis.

In acute obstructive cholecystitis the increased intraluminal pressure in the gallbladder is reduced by nonsteroid anti-inflammatory drugs which effectively relieve biliary pain. To investigate if such drugs influence the clinical course, a double-blind study was performed in which indomethacin (suppositories 75 mg b.d.) was tested against placebo in 34 patients with acute obstructive cholecystitis. During the 3-day treatment period both the indomethacin and the placebo group improved significantly as regards pyrexia, pain, abdominal tenderness and leukocytosis. The indomethacin group showed significantly greater improvement than the placebo group in temperature, pain and white blood cell count on day 1, and significantly greater reduction of abdominal tenderness on day 2. The serum bilirubin fell significantly during the 3-day period in the indomethacin, but not the placebo group. The hospital stay in cases without early surgery was significantly shorter in the indomethacin group (5.4 vs. 8.5 days). Because of its favourable effect on the clinical course of acute cholecystitis, rectally administered indomethacin is useful for patients awaiting operation or scheduled for later elective surgery.

Acute Disease↗
PubMed1991

Stabilization of recombinant proteins from proteolytic degradation in Escherichia coli using a dual affinity fusion strategy.

A dual affinity fusion approach has been used to study the expression and secretion of labile recombinant proteins in Escherichia coli. Here we show that three small eukaryotic proteins (human proinsulin, a thioredoxin homologous domain of rat protein disulfide isomerase, and the extracellular domain of the alpha 1.2-chain of a human T-cell receptor) are stabilized in vivo using a dual affinity fusion strategy, where the gene encoding the desired product is fused between two genes encoding two different affinity domains. Relatively high yields of full-length product were obtained for all three proteins as compared to when fused to a single fusion partner. Despite the use of a signal peptide, significant amounts of the disulfide protein isomerase and T-cell receptor gene products were maintained in the cytoplasm, while the proinsulin fusion was efficiently secreted to the periplasm. Interestingly, the E. coli heat shock proteins DnaK and GroEL were associated with the fusion proteins isolated from the cytoplasm.

Animals↗