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Biomedical subjects

B Nilsson

Publications and source records attributed to B Nilsson.

At least 523 records · Page 29Linked to original sources

Piroxicam in the treatment of primary dysmenorrhea.

In double-blind, crossover studies, piroxicam was compared with naproxen sodium and with placebo. The different parameters studied were pain intensity, patient's opinion of the drugs tested, complementary pharmacological treatment, ability to work, overall effect, treatment preference, and side effects. It was concluded that piroxicam was comparable to naproxen sodium and that piroxicam was significantly better than placebo, as regards these parameters. It was also concluded that piroxicam has an effect equivalent to that of naproxen sodium, an accepted treatment for dysmenorrhea.

Adolescent↗

Guaiac tests for detection of occult faecal blood loss in patients with endoscopically verified colonic polyps.

To evaluate the sensitivity of guaiac tests for colonic polyps, two tests were made on occult blood in faeces--Hemoccult II and Fecatwin-S--from 625 and 549 patients, respectively, referred for colonoscopy. Polyps were found in 212 and 194 patients, and these had one or more tests positive in 41% (Hemoccult II) and 48% (Fecatwin-S). The incidence of positive tests was greater for polyps situated in the transverse, descending, and sigmoid colon; for polyps with a stalk, villous elements, and dysplasia; and especially for large polyps. Although size was the most important factor for the bleeding tendency, at least one third of patients with polyps over 10 mm in diameter had no positive guaiac reactions. In patients at high risk of developing polyps, therefore, these tests cannot replace, but may well be supplementary to, radiography with double-contrast technique and colonoscopy.

Adolescent↗

Thirty-year follow-up of ankle fractures.

The natural course of ankle fractures was studied in 143 patients treated by closed methods. The average time elapsing from fracture to follow-up was 29 years. Eighty-two per cent had no radiographic signs of arthrosis; 83 per cent were free of symptoms. The most common fracture, supination eversion Stage II (49 cases), gave rise to minimal signs of arthrosis in only one patient, who had moderate symptoms. The suggestion that all ankle fractures must be perfectly reduced is not supported by the findings of the present study.

Adult↗

Effect of platelet inhibition on experimental venous thrombosis in the rabbit.

An experimental model, based on a combination of endothelial damage and flow reduction, was used to induce thrombosis of the jugular vein in rabbits. The influence of ibuprofen, a cyclooxygenase inhibitor, was compared with that of dextran 70, which influences platelets, thrombus structure and flow. Albumin was used as a control of the volume-expanding effect of dextran. Ibuprofen was administered intravenously during the induction of thrombosis, and dextran and albumin were given 3 hours before the surgical procedure. Control rabbits received only Ringer's lactate. Dextran, but neither ibuprofen nor albumin, significantly reduced the incidence of thrombosis, though thrombus weight was not influenced. The data indicated that the effect of dextran in this model probably is primarily exerted via alteration of thrombus structure, and not by altered platelet function or hemodilution. The role of platelets in the initial development of thrombosis in this model thus may be questioned.

Albumins↗

An analysis of factors predisposing to chronic graft-versus-host disease.

Among 75 consecutive allogeneic bone marrow transplant recipients, 24 developed chronic graft-versus-host disease (GVHD), which was diagnosed from day 31 to day 368 after transplantation. Eight (33%) patients had more extensive chronic GVHD, and five patients died. The actuarial incidence of chronic GVHD was 48% at 400 days. A number of factors were analyzed for their association with chronic GVHD. Recipients of marrow from donors over 17 years of age had an actuarial incidence of chronic GVHD at 400 days of 74%, compared with 27% if the donors were under 17 years of age (log-rank test on survival curves, p less than 0.001). Other factors that appeared to predispose for chronic GVHD in bivariate analysis were recipient age above 17 years (p less than 0.02), treatment with donor unirradiated buffy-coat cells (p less than 0.01), grade-II-IV acute GVHD (p less than 0.01), and a preceding cytomegalovirus (CMV) infection (p less than 0.01). In multi-variate analysis, however, only donor age above 17 years, treatment with donor buffy-coat cells, and grade-II-IV acute GVHD were significantly associated with chronic GVHD. The possible role of CMV infection in the development of chronic GVHD is discussed.

Anemia, Aplastic↗

Prognostic information from cytogenetic analysis in chronic B-lymphocytic leukemia and leukemic immunocytoma.

Fifty-five patients with a clonal expansion of B lymphocytes in the peripheral blood were studied. According to the Kiel classification, 22 patients had chronic lymphocytic leukemia (CLL), 29 had immunocytoma (IC), two had prolymphocytic leukemia, and one had centrocytic lymphoma; one was not subclassified. Cytogenetic studies after B cell mitogen stimulation showed that six patients had an extra chromosome 12 as the sole abnormality. Another ten patients had an extra chromosome 12 together with other abnormalities. One patient had dup(12). Fifteen patients showed clonal aberrations without +12. Eleven patients showed only normal metaphases, and 12 patients were not evaluated cytogenetically. The cytogenetic subgroup pattern did not distinguish between CLL and IC patients. There was no significant difference between the CLL and IC groups as regards clinical findings and prognosis. However, the cytogenetic typing proved to be of prognostic significance. Increasing numbers of chromosomal aberrations within the cell clone were significantly associated with a poorer prognosis, ie, with impairment of survival (P = .04) and therapy-free survival (P less than 10(-4]. Patients with complex karyotypes (at least clonal aberrations) showed the poorest survival (P = .007). Patients with +12 required treatment earlier than patients with a normal karyotype (P = .01) and patients with karyotypic changes other than +12 (P = .006). These latter differences were even more pronounced when only IC patients were considered (P = .005 and P = .002, respectively). A multivariate analysis revealed that +12 was as strong an indicator of poor survival as advanced Rai or Binet stages and a stronger predictor of therapy-demanding disease.

Adult↗

In vivo evaluation of the acute thrombogenicity of the modified human umbilical vein and autologous artery.

With the aim to evaluate acute thrombogenicity, segments of human umbilical vein grafts (Dardik Biograft, Meadox Medicals, Inc., Oakland, N.J.), nonheparinized, heparin-alcohol-treated, or covalently heparinized, were implanted into the carotid arteries of sheep. Autologous carotid arteries were used as control grafts. Flow was restricted to 25 ml/min. Accumulation of autologous 32P-labeled platelets was registered at both anastomotic and midgraft regions for 240 minutes. At the end of the perfusion period, grafts were removed, opened longitudinally, and the thrombus-free surface (TFS) and thrombus weight determined. The ex vivo determinations showed good correlation with results obtained with in vivo registration. In vivo accumulation of platelets was significantly larger in nonheparinized human umbilical vein grafts compared with heparin-alcohol treated grafts. Covalently heparinized grafts showed a tendency toward lower radioactive values, but visual examination after perfusion revealed areas of "intimal" damage with thrombotic deposits, probably caused by heparinization procedure. Autologous arteries showed the largest TFS and the smallest thrombi. Platelet accumulation in autologous arteries decreased almost to reference values after an initial rapid increase. In conclusion, heparin-alcohol treatment of human umbilical vein grafts reduces acute thrombogenicity. Although covalent heparin bonding seems to act in the same way, the fragility of the graft appears to preclude use of this method. Autologous arteries exhibit excellent antithrombotic characteristics.

Acute Disease↗

Structural studies on the O-glycosidically linked carbohydrate chains of glucoamylase G1 from Aspergillus niger.

Glucoamylase G1 from Aspergillus niger contains an unusual type of carbohydrate-protein linkage, involving mannose O-glycosidically linked to serine and threonine. The majority of the neutral oligosaccharides of glucoamylase G1 are located in a region of about 70 amino acid residues which carries about 35 oligosaccharide units [(1983) Carlsberg Res. Commun. 48, 517-527]. Structural analysis was performed on the O-linked carbohydrates of a tryptic fragment from glucoamylase G1 comprising the segment characterized by a high degree of glycosylation. The carbohydrate structures released by trifluoroacetolysis were elucidated using sugar analysis, methylation analysis, mass spectrometry, chromium trioxide oxidation, digestion with alpha-mannosidase and 1H-NMR spectroscopy. The following structures could be identified. (formula; see text)

Aspergillus niger↗

Human uterine fluid, examined in undiluted samples for osmolarity and the concentrations of inorganic ions, albumin, glucose, and urea.

Human uterine fluid and serum, when analyzed, had the same osmolarity. Both the total cation concentration and that of albumin were lower in uterine fluid than in serum. Decreased cation concentration is probably a regulatory mechanism maintaining electroneutrality in uterine fluid when the protein concentration is decreased, since protein molecules have multiple negative charges. Compared with their serum values, concentrations of potassium were high, and those of sodium and calcium were low. Concentrations of potassium and calcium in uterine fluid were found to vary cyclically, both having lower values at midcycle than in the proliferative and luteal phases. The concentrations of chloride, urea, glucose, and fructose in uterine fluid did not differ significantly from those in serum. A possible influence of the ionic composition of uterine fluid on sperm migration at midcycle and on the implantation process in the luteal phase was also considered.

Albumins↗

Purification and characterization of a mannose-containing disaccharide obtained from human pregnancy urine. A new immunoregulatory saccharide.

Endogenous mammalian lectin-like sugar-binding molecules have been previously described that have immunoregulatory properties. Further, the addition of defined simple saccharides to lymphocyte cultures has been shown to inhibit a variety of in vitro lymphocyte functions, presumably because these sugars are able to compete with the binding of endogenous lectins to critical membrane receptors. In this report, we describe the isolation and characterization of a D-mannose-containing disaccharide in human pregnancy urine that inhibits the proliferative response of human T lymphocytes. The inhibitory disaccharide was purified to homogeneity by sequential steps including affinity chromatography on immobilized concanavalin A and molecular sizing on Sephadex G-75 and then Fractogel 40S columns, with final purification on high-performance thin-layer chromatography. By mass spectrometry of the purified material as its permethylated derivative, the deduced structure of this compound was alpha-D-Manp 1-6-D-Man. To confirm that this disaccharide was in fact immunosuppressive, an identical disaccharide was prepared by sequential digestion of yeast cell wall polysaccharide. The urinary and yeast disaccharides had identical immunosuppressive properties. It has been previously reported that D-mannose is inhibitory for antigen-specific proliferative assays in the range of 10-50 mM. The purified alpha-D-Manp 1-6-D-Man disaccharide was inhibitory at 100-fold-lower concentrations. Further, while D-mannose inhibits T cell proliferation when added at anytime up to 24 h before harvest of a 6-d lymphocyte culture, alpha-D-Manp 1-6-D-Man disaccharide was inhibitory only if added at the initiation of culture and had no inhibitory effect if added just 24 h later. These data support the concept that simple sugar compounds can exhibit marked immunoregulatory activity in vitro. The impact of these molecules on the regulation of immune responses in vivo is unknown, as is their precise mechanism of action, but structural and chemical identification should now permit a detailed analysis of these issues.

Chromatography, Affinity↗

Simplified assays of hemolytic activity of the classical and alternative complement pathways.

Simplified hemolytic assays for the classical (CP) and alternative (AP) pathways of complement (C) were developed. The CP function was tested with sensitized sheep erythrocytes in a diluent containing Ca2+ and Mg2+, while AP was tested with unsensitized rabbit erythrocytes in a diluent containing Mg2+-EGTA. In contrast to the commonly used hemolytic titration (CH50) assays, the present techniques tested the activity in reaction mixtures containing C at final dilutions which would not affect its function. These ranges fell between 1/1 and approximately 1/20 for CP and between 1/1 and approximately 1/3 for AP. With the adopted assay techniques single aliquots of serum were tested at single final dilutions of 1/8 for CP and 1/2 for AP, in the presence of excess target cells. Hemolysis was allowed to take place at 37 degrees C for 20 min. The number of cells lysed by CP and AP under these conditions was directly proportional to the dose of serum and unaffected by the presence of a large excess of target cells. Each pathway was tested independently of the other. Serum C levels, measured as described, correlated strongly with those determined by standard hemolytic titration (CH50) assays. The modified assays should offer less laborious alternatives for the functional assay of C than current routine procedures.

Animals↗

Specific binding of 17 beta-estradiol in the human thymus.

Many observations suggest that estrogenic preparations can depress cell-mediated immune reactions. Since cell-mediated immunity is thymus-dependent, the estrogen-binding properties of human and mouse thymus tissue were studied with the use of an aqueous two-phase separation system. A high-affinity and low-capacity estrogen binding was found in human thymus tissue from six prepubertal children of both sexes and two grown women. A similar specific binding was found in the mouse thymus and in the human uterus. The association constant (Ka) for the binding in the human thymus was 16.01 +/- 8.98 X 10(9)M-1. The human uterus, which is known to possess estrogen receptors, had Ka values in the same range. The binding seems to be located in the reticuloepithelial cells of the thymus. Data suggest that the human thymus is a target organ for estrogens, which may influence lymphocyte function during therapy.

Adult↗

Immunochemical studies on blood groups. Purification and characterization of radioactive 3H-reduced di- to hexasaccharides produced by alkaline beta-elimination-borohydride 3H reduction of Smith degraded blood group A active glycoproteins.

Treatment of blood group A active glycoprotein from human ovarian cyst fluid by one stage of Smith degradation followed by alkaline beta-elimination in the presence of NaB[ 3H4 ] (Carlson degradation) liberated tritiated oligosaccharide alditols. The carbohydrate mixture was fractionated by gel filtration, elution from charcoal, paper chromatography, and high pressure liquid chromatography. Structures were established based on sugar composition, periodate oxidation, methylation analysis, and analysis of oligosaccharide alditols as permethylated and N-trifluoroacetylated derivatives by gas-liquid chromatography-mass spectrometry. The following structures have been deduced: Gal beta 1----3GalNAc-ol, GlcNAc beta 1---- 6GalNAc -ol, Gal beta 1---- 3GlcNAc beta 1----6(3-deoxy)GalNAc-ol, Gal beta 1---- 3GlcNAc beta 1---- 6GalNAc -ol, Gal beta 1----4GlcNAc beta 1---- 6GalNAc -ol, GlcNAc beta 1----3Gal beta 1----3GalNAc-ol, Gal beta 1----3[GlcNAc beta 1----6]GalNAc-ol, Gal beta 1----3[Gal beta 1----4GlcNAc beta 1----6]GalNAc-ol, Gal beta 1---- 3GlcNAc beta 1----3Gal beta 1----3GalNAc-ol, GlcNAc beta 1----3Gal beta 1----4GlcNAc beta 1---- 6GalNAc -ol, GlcNAc beta 1----3Gal beta 1----3[Gal beta 1----4GlcNAc beta 1----6]GalNAc-ol, Gal beta 1---- 3GlcNAc beta 1----3Gal beta 1---- 3GlcNAc beta 1----3Gal beta 1----3Gal beta 1----3GalNAc-ol, Gal beta 1---- 3GlcNAc beta 1----3[Gal beta 1----4GlcNAc beta 1----6]Gal beta 1----3GalNAc-ol, Gal beta 1---- 3GlcNAc beta 1----3Gal beta 1----3[Gal beta 1----4GlcNAc beta 1----6]GalNAc-ol. The smaller structures represent pieces of the larger structures. Together they provide direct evidence for the core structure of the carbohydrate side chains in the blood group substances as proposed by K. O. Lloyd and E. A. Kabat [1968) Proc. Natl. Acad. Sci. U.S.A. 61, 1470-1477). Oligosaccharides previously isolated after Carlson degradation of intact human ovarian cyst fluid HLeb , Lea, and B substances and from human and horse B substances contained various alpha-linked L- fucopyranose and alpha-linked Gal substitutions on the composite structure.(ABSTRACT TRUNCATED AT 400 WORDS)

ABO Blood-Group System↗

Is breast cancer a curable disease? A study of 14,731 women with breast cancer from the Cancer Registry of Norway.

The question whether breast cancer is curable remains controversial. Late recurrences and death from the disease are not infrequent. Long term follow-up of a large patient population is necessary to study this issue. The authors report a study of 14,731 cases of breast cancer reported to the Cancer Registry of Norway with follow-up times ranging from 5 to 18 years. A model in which the logarithms of the survival times were assumed to be normally distributed, the lognormal model, fitted the data well for individual stages, age groups, and periods of treatment. The cured fraction, i.e., consisting of those only subject to normal mortality risks, was estimated from the model to 35 +/- 1% standard error. In Stages 1, 2, 3, and 4 it was 54 +/- 3%, 27 +/- 1%, 19 +/- 2%, and 2 +/- 1%, respectively. It is concluded, however, that the estimated cure rate in Stages 3 and 4 should be regarded with caution in view of the methodological problems involved in the analysis and the small number of patients with long follow-up. The estimated cured fraction in both the individual stages and in the entire material was significantly higher in patients younger than 55 years of age than in older patients. The median survival of non-cured patients was estimated to be 3.6 years for the entire material. In Stage 1, 2, 3, and 4 it was 7.6 years, 3.4 years, 2.1 years, and 0.7 years, respectively. The lognormal model seems to be a good approximation of breast cancer survival. The model is consistent both with late excess mortality and with the presence of a cured fraction. It is noteworthy that an excess mortality was observed during the whole follow-up period. Extrapolations from the model should therefore be cautiously judged until supported by observed data.

Aged↗

Complete sequence of the staphylococcal gene encoding protein A. A gene evolved through multiple duplications.

The gene coding for protein A from Staphylococcus aureus has been isolated by molecular cloning, and a subclone containing an 1.8-kilobase insert was found to give a functional protein A in Escherichia coli. The complete nucleotide sequence of the insert, including the structural gene and the 5' and 3' flanking sequences, has been determined. Starting from a TTG initiator codon, an open reading frame comprising 1527 nucleotides gives a preprotein of 509 amino acids and a predicted Mr = 58,703. The structural gene is flanked on both sides by palindromic structures followed by a stretch of T residues, suggesting transcriptional termination signals. Thus, it appears that protein A is translated from a monocistronic mRNA. The sequence reveals extensive internal homologies involving a 58-amino acid unit, responsible for IgG binding, repeated 5 times and an 8-amino acid unit, possibly responsible for binding to the cell wall of S. aureus, repeated 12 times. Comparisons between the repeated regions show a marked preference for silent mutations, indicating an evolutionary pressure to keep the amino acid sequence preserved. The structure of the gene also suggests how the gene has evolved.

Amino Acid Sequence↗

Region X, the cell-wall-attachment part of staphylococcal protein A.

The sequence of region X of staphylococcal protein A has been determined. The hypothesis has been put forward that this region spans the Staphylococcus aureus cell wall and is responsible for the binding to the peptidoglycan. The primary amino acid sequence of region X was determined for two strains exhibiting cell-wall-bound protein A, Cowan I and 8325-4. The sequence determination of the Cowan I material is partial and was performed by Edman degradation, in contrast to the sequence of the 8325-4 material which was completely analyzed by nucleotide sequencing of the corresponding gene. The region consists of two structurally different domains, a highly repetitive region (Xr), with an octapeptide structure repeated approximately 12 times, and a C-terminal domain (Xc) with an unique sequence. A comparison between the two strains reveals a high mutual homology as well as a high internal homology between the octapeptide structures. Six out of eight amino acids are identical in the repetition of this structure throughout region Xr in both proteins and the other two are changed in a rather regular pattern.

Amino Acid Sequence↗