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Biomedical subjects

B Nilsson

Publications and source records attributed to B Nilsson.

At least 271 records · Page 15Linked to original sources

Tricuspid valve insufficiency as a complication of endomyocardial biopsy.

The purpose of this study was to investigate the occurrence of major tricuspid insufficiency caused by endomyocardial biopsy in heart transplant recipients. Endomyocardial biopsy was used for the detection of rejection and Doppler echocardiography was performed at regular intervals. Six of 96 heart transplant patients (6.3%) had sudden appearance of large tricuspid regurgitation, all of which were directly related to a preceding biopsy. Chordal tissue was identified histologically in biopsy samples of all six patients. All patients developed symptoms of right ventricular failure which was confirmed by right heart catheterization. Three patients subsequently underwent valvuloplasty for ruptured chordae tendineae of either of the three leaflets. Two of these three patients were free from symptoms during follow-up, but the third patient developed moderate tricuspid regurgitation and clinical symptoms. It is concluded that endomyocardial biopsy, although it is the most useful tool for detection of rejection, should be used with caution with regard to anatomical structures and the risk of damage to the tricuspid valve must not be neglected. It is also concluded that valvuloplasty of the tricuspid valve can be successfully performed in a transplanted heart.

Adolescent↗

Expression of intestinal alkaline phosphatase in human organs.

Human intestinal alkaline phosphatase was immunohistochemically identified and localized in the pancreas, liver and kidney by use of a monoclonal antibody specific for intestinal alkaline phosphatase isozyme and by amplified biotin-streptavidin staining. In all the examined organs, the intestinal isozyme was found to be localized in the epithelial cells of ducts: bile ducts in the liver, distal convoluted tubules and collecting tubules in the kidney and ducts in the secretory epithelium in the pancreas. In the liver the antibody also stained some sinus-lining cells. In all the examined organs the endothelial cells of the capillaries and some vessels were stained. By use of immunoelectron microscopy, intestinal alkaline phosphatase was, as expected, found to be localized to the microvillar region of the small intestine. The isozyme was abundantly expressed in the apical area of the microvilli and in membrane remnants in the fuzzy coat. Capillaries and vessels in the submucosa were also stained, as well as small vesicles in the endothelial cells. The present investigation demonstrates the expression and localization of the intestinal alkaline phosphatase in several organs, though previously believed to be expressed only in the intestine.

Alkaline Phosphatase↗

Blood transfusion in marrow graft recipients.

Of 182 consecutive patients undergoing allogeneic bone marrow transplantation (BMT), the relative numbers of those who received red blood cells (RBC), platelets (PLT), and granulocytes were 82%, 96%, and 26%, respectively. The transfused patients received an average of 1.26 (SD +/- 2.0) RBC units, 9.41 (SD +/- 13.2) PLT transfusions, and 0.33 (SD +/- 1.1) granulocyte concentrates per week per 50 kg body wt. in the period starting on the day of bone marrow transplantation (BMT) up to 60 days post BMT. The total number of units per transfused patient was 7.7 (range 1-63) RBC, 55.2 (range 2-394) PLT and 6.2 (range 1-36) granulocytes in the same period. Patients with grades II-IV acute graft-versus-host disease (GVHD) needed more RBC and PLT (p less than 0.001) than patients with grades 0-I acute GVHD. Patients with late engraftment required more granulocyte and PLT transfusion than those with early engraftment (p less than 0.05). Patients with high-risk malignancy had greater need for RBC and PLT than "low-risk patients" (p less than 0.02 and p less than 0.01), respectively). Patients with major ABO-incompatible donors showed a greater need for RBC than patients with minor ABO incompatibility (p = 0.02) or ABO identical donors (p = 0.01). Patients with relatively poor estimated survival required the most RBC and PLT.

ABO Blood-Group System↗

Interval cancer and survival in a randomized breast cancer screening trial in Stockholm.

The aim of the present study was to analyse the survival rate in a group of breast cancers detected in the intervals between screening examinations in relation to clinically detected cancers in a non-screened population. All interval and control cancers were recruited from a randomized controlled mammography screening trial in Stockholm. The overall survival up to eight years of observation was higher in 191 patients with interval cancers than in 142 control cancers (p = 0.01). There were no significant differences between the two groups with regard to tumor size, stage distribution, or mean age, though the interval group did have a larger proportion of younger women. The similarity was confirmed by multiple regression analysis. The overall survival stage by stage was consistently higher in interval cancers. The survival rate in the true interval cancers was similar to that for those found in retrospect to have been detectable or traceable at the time of screening. No correlation was found between the length of the interval and the survival of patients with interval cancers. These results contradict the hypothesis that a high growth rate is associated with a poorer prognosis and that interval cancers are a more aggressive form of breast neoplasia.

Adult↗

Mass spectrometry of high-mannose oligosaccharides after trifluoroacetolysis and periodate oxidation.

High-mannose oligosaccharides were treated with a mixture of trifluoroacetic acid and trifluoroacetic anhydride under conditions where reducing terminal N-acetylglucosamine residues are specifically degraded. The resulting mannose-containing products were, after further chemical modifications, analyzed by mass spectrometry in fast atom bombardment and electron ionization modes. Binding positions between monosaccharide residues were deduced from mass spectra of peracetylated compounds, which, prior to the derivatization, had been subjected to periodate oxidation and borodeuteride reduction.

Acetylation↗

Fusions to the 5' end of a gene encoding a two-domain analogue of staphylococcal protein A.

A novel gene fusion system has been constructed for fusions to the 5' end of gene zz, encoding a two-domain analogue of staphylococcal protein A designated ZZ. Four different genes were fused to the 5' end of zz, and their gene products were analyzed. One of the genes encodes a protein located intracellularly in Escherichia coli and the other three genes encode gene products destined for secretion across the cytoplasmic membrane by the presence of an amino terminal signal sequence. After production in E. coli, the fusion proteins were purified in a single step by IgG-affinity chromatography. The purified ZZ fusions could be used directly for amino terminal sequencing to confirm the start of translation of the intracellular product and the processing of the signal peptide of the translocated products. This is the first example of ZZ fusions to the C-terminus of gene products. To simplify the general use of fusions to the 5' end of zz, a new plasmid vector was constructed containing a multi restriction enzyme cloning linker and the lacZ' gene which enables screening for production in alpha-complementing supE strains of E. coli on indicator plates.

Amino Acid Sequence↗

Fusion proteins in biotechnology.

Gene fusion techniques allow the production of recombinant proteins featuring the combined characteristics of the parental products. Originally, these techniques were used to probe transcriptional and translational activity, to translocate proteins across cell membranes, and to facilitate the recovery of proteins. Recently, new applications have emerged in areas such as protein refolding, immunology, drug targeting and protein display. A slightly modified version of this review is also published in Current Opinion in Structural Biology 1992, 2:569-575.

Biotechnology↗

Prognostic significance of mucosal aneuploidy in stage Ta/T1 grade 3 carcinoma of the bladder.

In a prospective series of 71 patients with newly detected grade 3, stages Ta and T1 bladder carcinoma tumor characteristics, including the results of deoxyribonucleic acid (DNA) analysis as well as morphological and DNA characteristics of the grossly normal urothelium, were investigated and related to progression-free survival. The mean duration of followup was 57 months, with a minimum of 24 months. Of the 71 patients 24 underwent primary cystectomy, and 47 were conservatively treated with transurethral resection alone, or followed by instillation therapy or irradiation therapy. Of the cystectomy and conservatively treated patients 2 (8%) and 16 (34%), respectively, died of bladder carcinoma. Among the 47 conservatively treated patients tumor progression could not be predicted by the initial characteristics of tumor stage, papillary or nonpapillary growth, tumor multiplicity, tumor size, existence of 1 or multiple aneuploid cell populations, S phase value, carcinoma in situ and atypia or aneuploidy in the mucosal biopsies. Neither was progression predicted by the recurrence rate during year 1 of observation. However, a change to or persistent mucosal aneuploidy and a change to or persistent morphological abnormality of the mucosa during year 1 of observation were predictive for tumor progression (p = 0.001 and 0.045, respectively). When compared in stepwise regression analysis (Cox's proportional hazard model), DNA aneuploidy in the mucosa at 12 months after diagnosis was a highly significant predictor, whereas morphology added no further prognostic information. Therefore, progression is related to gross chromosomal abnormalities of the mucosa. High risk patients can be identified by evaluation of the grossly normal mucosa, which should be done as part of the initial diagnosis and during followup in conservatively treated patients with stages Ta and T1, grade 3 bladder carcinoma.

Adult↗

Stimulation of NK cell, T cell, and monocyte functions by the novel immunomodulator Linomide after autologous bone marrow transplantation. A pilot study in patients with acute myeloid leukemia.

Immunostimulatory therapy is at present considered after autologous bone marrow transplantation (ABMT) in order to mimic the allogeneic graft-versus-leukemia effect and thereby reduce the relapse rate. In a pilot study, five adults with acute myeloid leukemia were treated with the new immunomodulator Linomide post-ABMT. Linomide (0.3 mg/kg/week orally) was given in cycles of three weeks followed by three weeks of rest for up to six months. During treatment periods cyclic increases of CD56+CD3- and CD16+ NK cells were observed in parallel with enhanced cytotoxic activity of patient cells against both the NK-sensitive K562 and NK-resistant Daudi cell lines. A cyclic increase of CD14+ monocytic cells was also recorded. The proliferative responses of patient cells to PHA and allogeneic cells (MLC) were enhanced during Linomide therapy. The in vitro production of TNF alpha, IFN gamma, and IL-1 followed the same cyclic increase during treatment periods. Side effects were generally mild, and no harmful effects on engraftment were seen. Linomide therapy after ABMT thus induces a broad immunostimulation that offers a potential benefit with regard to leukemia-free survival.

Adjuvants, Immunologic↗

Detection and characterization of immunoconglutinins in patients with systemic lupus erythematosus (SLE): serial analysis in relation to disease course.

The levels of IgA, IgG and IgM immunoconglutinins (IK) were assessed in sera from 20 patients with SLE which were followed for 8-month periods. At the time of the exacerbation, IgG IKs were significantly increased to 226 +/- 90 arbitrary units (mean +/- s.e.m.) compared with both the minimum value of 75 +/- 28 in the SLE patients and with 31 +/- 2 in healthy controls (P < 0.05). There was no difference between SLE patients and controls in the levels of IgM and IgA IKs. Most of the SLE patients in this material showed maximal IgG IK levels before exacerbation, but there was no correlation between the clinical disease index and the levels of IgG IK. The specificity of IgG IKs showed a broad diversity for microtitre-fixed C3b, iC3b, C3c and C3dg. The antibodies were of IgG1, IgG3 and in two patients, IgG4 subclass. IgG IKs were correlated to the C3d/C3 ratio which suggested that the IK responses were secondary to C3 activation. In summary, unlike other conditions associated with complement activation where elevated IgM IKs are common, an increase in IgG IK levels was observed. It is possible that this diverging IK response contributes to the pathophysiology of the disease.

Antibody Specificity↗

Generation of iC3 at the interface between blood and gas.

Earlier studies have shown that C3 can be denatured when blood comes in contact with a polystyrene surface. This study was undertaken to see if similar denaturation of C3 occurs at the gas-plasma interface which is found in all kinds of oxygenator used during cardio-pulmonary operations. An in vitro system consisting of gas bubbling through human blood, serum or plasma was used. The generation of C3a, as an indicator of complement activation, and iC3 and iC3 fragments were monitored. Both C3a and iC3/iC3 fragments levels were increased during bubbling. In contrast to the C3a level, no reduction in iC3/iC3 fragments formation was seen in the presence of EDTA, indicating that it was independent of complement activation. The rate of iC3/iC3 fragments generation was unaffected by the composition of the gas (pure oxygen, pure nitrogen or air), suggesting that the denaturation of C3 indeed occurred at the serum-gas interface. C3 and iC3/iC3 fragments were isolated from bubbled EDTA-chelated serum by PEG precipitation and chromatography on FPLC, using a Mono S column and detected by two ELISAs, specific for native C3 and iC3/iC3 fragments. After 240 min approximately 20% of the total amount of C3 consisted of intact iC3 and it was confirmed that this population bound to human erythrocytes.

Blood↗

DNA analysis in predicting survival of irradiated patients with transitional cell carcinoma of bladder.

A total of 115 patients with invasive transitional cell carcinoma of the bladder underwent radical radiotherapy between 1975 and 1986 and were followed up until the end of 1990. Apart from routine clinical observations, flow cytometric DNA measurements made on fresh tumour material were available for analysis. Actuarial cancer-free survival controlling for response to treatment was analysed with the log-rank test, bivariate and multivariate analyses using Cox's stepwise regression model on probable prognostic factors. The overall actuarial 5-year cancer-free survival rate was 30%. Survival was significantly correlated with response to treatment: 59% for patients with complete regression and 5% for those with residual tumour. Prognostic factors that significantly correlated with death from cancer were advanced stage, large size, incomplete resection, ureteric obstruction, anaemia, carcinoma in situ grade 3 and occurrence of more than one aneuploid cell population. However, only 3 of these factors were of independent power in the multivariate analysis: stage, size and carcinoma in situ. Of 21 patients with a history of primary or secondary carcinoma in situ, 19 died from cancer during follow-up: 18 of the 21 patients had tumours that were aneuploid with more than one aneuploid cell population. It is concluded that curative radiotherapy can be successful only in patients with less advanced tumours assessed according to clinical stage and size, aneuploid tumours with not more than one aneuploid cell line, no carcinoma in situ, no ureteric obstruction, and in whom a complete transurethral resection of the exophytic tumour is possible.

Aged↗

Clinical examination, mammographic findings and cytological diagnosis in patients with breast disorders. Results of 9 years' follow-up.

In January through March 1978, 482 consecutive patients sought advice and examination for different kinds of breast disorders at the Breast Unit of Radiumhemmet; 171 of them (32.8%) came without any prior known medical consultation. All patients were seen by a doctor and examined clinically; 385 underwent mammography and 196 fine-needle aspiration for cytology. Combined clinical and mammographic examination showed an estimated specificity with respect to 'breasts with no need of follow-up' of 77%. The corresponding sensitivity was 88%. Fine-needle aspirations showed an estimated specificity and sensitivity of 96% and 88% respectively. In the total material 26 malignant cases were found, of which 16 cancers were detected at the first examination. During a follow-up period of nine years, 10 additional breast cancers were found in the national cancer registry. This number could be compared to the expected number of 6.6 (SIR 1.52, 0.73-2.79) breast cancer cases if the studied women had had the same standardized incidence as the total female Swedish population. The mean number of visits to the Breast Unit was 1.6 for the 466 patients with benign disorders, of whom 322 had no need of follow-up. The mean follow-up time for these 482 patients was 113 days. During the follow-up time, 22 patients died. Ten patients, one of them with a breast cancer diagnosed, emigrated.

Adolescent↗

A randomized study of long-term out-patient treatment in alcoholics. Psychiatric treatment versus multimodal behavioural therapy, during 1 versus 2 years of treatment.

Seventy-two alcoholic patients (60 men and 12 women) were randomized into four groups who received psychiatric treatment (PT) or multimodal behavioural therapy (MBT), for either 1 or 2 years. PT was based on psychodynamic principles, and MBT is a cognitive-behavioural treatment. The patients accepting treatment had a mean age of 37 +/- 9 years, and they were socially stable. There was no difference in attrition rate (35%) in relation to therapy and length of treatment. The rate of favourable drinking outcome during the third year was similar in all four alternatives, at 40-44%. A favourable drinking outcome was predicted by a better initial psychic status and few psychiatric symptoms at intake. In PT patients a favourable outcome was more strongly related to a better psychic status than in MBT patients (P = 0.58). The mean number of sessions, 23, did not differ in relation to outcome. The main conclusion from this study is that there were only small and inconclusive differences between the therapies of different types and different duration.

Alcoholism↗

Photographic densitometry for quantitative DNA analysis of cytologic and histologic specimens.

We found that photographic densitometry (PD) is a useful technique for quantitative determinations of nuclear DNA content in clinical tumor material. Optimum conditions for the use of PD in clinical cytology and histopathology were worked out. A quantitative evaluation of the method was performed, particularly with respect to errors that may appear when measuring clinical tumor material. Our study showed that PD offers accurate DNA measurements in cytologic and histologic specimens. Ploidy level determinations in tumor cell populations in clinical material could be as accurately performed with PD as with scanning microspectrophotometry (SMP). Nuclear DNA content of individual cells as determined by PD correlated highly with nuclear DNA content determined by SMP (correlation coefficient, 0.96). Since the PD method is less influenced by background variation than are other image techniques (due to measurement of a photographic image), it is particularly useful in measurement of histopathologic sections, in which the background variation can introduce considerable errors. The method is also valuable with clinical cytologic smears, in which the presence of blood and other material disturbs the background. PD represents a valid complement to scanning microspectrophotometry and TV imaging systems, particularly for DNA analysis of tissue sections. Moreover, it can be applied easily in the clinical routine. Relevant tissue areas are selected and photographed by the pathologist or cytopathologist, and the measurement is performed by a laboratory technician.

Cell Nucleus↗

A procedure for the analysis by mass spectrometry of the structure of oligosaccharides from high-mannose glycoproteins.

A strategy, based on mass spectrometry, for analysis of the structure of oligosaccharides obtained from high-mannose glycoproteins, is described. The oligosaccharides are analysed first by f.a.b.-m.s. as the acetylated alditols, then O-deacetylated, oxidised with periodate, and reduced with borodeuteride. The products are analysed further by f.a.b.-m.s. after acetylation and subsequently by both f.a.b.- and e.i.-m.s. after methylation. The entire procedure is carried out on the same sample and the data allow assignment of the positions of all of the glycosidic linkages, including those of the branched residues. Individual components in mixtures of isomeric compounds can often be identified from f.a.b.-m.s. by their molecular weights after periodate oxidation.

Carbohydrate Sequence↗

Structural analysis of the N-linked oligosaccharides from murine glycophorin.

Glycophorins, isolated from BALB/c mouse erythrocytes, were degraded under mild and strong reductive alkaline conditions and the N-linked oligosaccharides were isolated as alditols. The oligosaccharide alditols were fractionated and purified using gel filtration, concanavalin A-Sepharose affinity chromatography, and high-performance ion-exchange chromatography. Structural analysis was carried out by chemical analyses, periodate oxidation in combination with fast atom bombardment mass spectrometry, and 500-MHz 1H NMR spectroscopy. The results revealed the presence of sialylated biantennary, triantennary, and tetraantennary complex type oligosaccharides, all fucosylated at the innermost N-acetylglucosamine residue. The tri- and tetraantennary oligosaccharide-containing fractions also contained species elongated by one and/or two N-acetyllactosamine (-3Gal beta 1-4GlcNAc beta 1-) sequences. The N-linked oligosaccharides were shown to be combined only with one (the low molecular weight) of the two mouse glycophorins.

Animals↗