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Biomedical subjects

M Andersson

Publications and source records attributed to M Andersson.

At least 343 records · Page 19Linked to original sources

Identification of a human lactoferrin-binding protein in Staphylococcus aureus.

Human lactoferrin (HLf) is an iron-binding protein with antimicrobial activity that is present in high concentrations in milk and various exocrine secretions. HLf is also an acute-phase protein secreted by polymorphonuclear leucocytes, and its binding to a large number of clinical isolates of Staphylococcus aureus has been described recently from our laboratory. We have now characterised the HLf-staphylococcal interaction in S. aureus strain MAS-89. The binding of 125I-HLf to strain MAS-89 reached saturation in less than 90 min and was maximal between pH 4 and 9. Unlabelled HLf displaced 125I-HLf binding. Various plasma and subepithelial matrix proteins, such as IgG, fibrinogen, fibronectin, collagen and laminin, which are known to interact specifically with S. aureus, did not interfere with HLf binding. A Scatchard plot was non-linear; this implied a low affinity (1.55 x 10(7) L/mol) and a high affinity (2.70 x 10(8) L/mol) binding mechanism. We estimated that there were c. 5700 HLf binding sites/cell. The staphylococcal HLf-binding protein (HLf-BP) was partially susceptible to proteolytic enzymes or periodate treatment and was resistant to glycosidases. An active HLf-BP with an apparent Mr of c. 450 Kda was isolated from strain MAS-89 cell lysate by ion-exchange chromatography on Q-sepharose. In SDS-PAGE, the reduced HLf-BP was resolved into two components of 67 and 62 Kda. The two components demonstrated a positive reaction with HLf-HRPO in a Western blot. These data establish that there is a specific receptor for HLf in S. aureus.

Bacterial Proteins↗

Genetic, hormonal and behavioural influence on spontaneously developing arthritis in normal mice.

DBA/1 male mice develop arthritis spontaneously at the age of 4 months. The affected joints show cell-rich pannus formation without T cell infiltration and only limited MHC class II expression. Specific pathogen-free DBA/1 mice from different sources developed the same disease. Analyses of inbred mouse strains with various genetic backgrounds and F1 hybrids revealed that the disease is genetically dependent of DBA/1 recessive genes. However, F1 hybrids between DBA/1 and BXSB spontaneously developed arthritis with earlier onset than DBA/1 mice, suggesting that the BXSB autoimmune gene background had both permissive and contributing effects on the development of arthritis. The complete male preponderance for disease susceptibility was investigated by castration and testosterone treatment of DBA/1 males. No arthritis developed after castration and disease susceptibility was restored by testosterone treatment. Arthritis developed only where more than two males were kept in cages, suggesting an influence by aggressive behaviour. Thus, the spontaneous development of arthritis is dependent on hormonal and behavioural mediated effects and differs from experimental models for rheumatoid arthritis such as type II collagen-induced arthritis and pristane-induced arthritis. We conclude that the spontaneously developing arthritis in the normal DBA/1 strain may be more useful as a disease model for osteoarthritis than for rheumatoid arthritis.

Animals↗

Cardiac conduction in patients with hypercalcaemia due to primary hyperparathyroidism.

OBJECTIVE: To assess whether hypercalcaemia due to primary hyperparathyroidism is associated with significant cardiac arrhythmias. DESIGN AND PARTICIPANTS: The prevalence of cardiac arrhythmias and conduction disturbances was evaluated by 12-lead ECG and 24-hour long-term ECG during pre-surgical hypercalcaemia and after post-surgical normalization of serum calcium values in 20 patients with primary hyperparathyroidism. RESULTS: After surgery, mean +/- SD calcium levels decreased from 2.85 +/- 0.1 to 2.40 +/- 0.1 mmol/l (P < 0.001). There was a significant increase in QT-intervals (0.36 +/- 0.05 vs 0.39 +/- 0.05) and QTc-intervals (0.38 +/- 0.04 vs 0.42 +/- 0.03) after surgery (P < 0.01). Long-term ECG showed no change in the minimal heart rate 47 +/- 8 vs 48 +/- 7 beats/min or in the longest RR interval 1.6 +/- 0.5 vs 1.6 +/- 0.5 s (P NS). There was no difference in the prevalence of supraventricular or ventricular arrhythmias. No episode of high-grade AV-block was observed before surgery. Circadian heart rate rhythm did not change between investigations. CONCLUSIONS: It is concluded that moderate hypercalcaemia, in spite of causing a shortening of the repolarization phase (QT-interval), has no clinically significant effect on cardiac conduction.

Adult↗

Binding characteristics of the thyroid hormone receptor homo- and heterodimers to consensus AGGTCA repeat motifs.

Previous studies have shown that thyroid hormone receptors can form homo- and heterodimeric complexes when binding to response elements. We report here the binding characteristics of thyroid hormone receptor (TR) homo- and heterodimers binding to synthetic oligonucleotides with directly and palindromically repeated consensus motifs (AGGTCA). Binding assays showed that TR homodimer formation on DNA had a low specificity and cooperativity, and very fast off rates. In contrast, TRs and retinoic acid receptors readily formed heterodimers with higher specificity and affinity on direct repeats of the AGGTCA motif spaced by four or five nucleotides, although these heterodimer/DNA complexes were only moderately stable when compared to DNA-bound TR/retinoid X receptor heterodimers. Also, TR/retinoic acid receptor heteromeric binding to other elements, including the synthetic T3RE-pal element, was of low specificity. These biochemical results suggest that TRs are unlikely to regulate transcription as homodimers in vivo, and that TR heterodimers mediate the effects of thyroid hormone.

Animals↗

Flow cytometric analysis of reticulocytes using an RNA-binding fluorochrome.

The reticulocyte count is an important parameter in the diagnosis of anaemia. The commonly used microscopic counting technique is, however, laborious and hampered by poor precision and low sensitivity. An alternative method has recently been developed, which is based on flow cytometric identification and quantification of reticulocytes after staining with an RNA-binding fluorochrome, thiazol orange. The two methods were compared both in a sample of healthy individuals and in patient specimens. The correlation between the methods was good, but the flow cytometric analysis consistently gave values approximately 1.5 times higher (reticulocytes in per cent of erythrocytes) than the microscopic technique. The coefficient of variation was significantly lower for the flow cytometric technique. Reference values for the reticulocyte count were determined and the effects of storage of specimens were evaluated. It is concluded that flow cytometric analysis of reticulocytes is more sensitive and has a better precision that the standard microscopic procedure.

Anemia, Aplastic↗

Carcinogenic effects of adjuvant tamoxifen treatment and radiotherapy for early breast cancer.

The occurrence of new primary tumours among postmenopausal patients with primary breast cancer subsequent to adjuvant treatment in Denmark was assessed by linkage to the cancer registry. Following primary surgery, patients in low risk of recurrence (n = 1,828) received no further treatment while patients in high risk randomly received either adjuvant radiotherapy alone (n = 846) or radiotherapy + tamoxifen 30 mg daily for 48 weeks (n = 864). With a median follow-up of 8 years, the incidence of tumours in the contralateral breast was similar among tamoxifen-treated, and non-treated high-risk patients even after adjusting for tumours arising within the first year. The standardized incidence ratio for endometrial cancer was 1.9 (95% confidence interval 0.8-3.9) among tamoxifen treated, the cumulative incidence 1% compared to 0.3% among non-treated patients (p = 0.11). The cumulative risk of non-lymphocytic leukaemia was 0.9% and 0.1% among irradiated and non-irradiated patients respectively (p = 0.4). Prolonged follow-up of tamoxifen-treated patients with regard to new tumours is recommended.

Breast Neoplasms↗

Adverse effects of perioperative blood transfusion in patients with colorectal cancer.

OBJECTIVE: To assess the effects of perioperative blood transfusion on cancer related survival and infective complications after radical operations for colorectal cancer. DESIGN: Retrospective study. SETTING: District hospital in Sweden. SUBJECTS: 217 patients who fulfilled the criteria for inclusion, out of 392 consecutive patients operated on for colorectal cancer between 1975 and 1979. MAIN OUTCOME MEASURES: Morbidity and cancer related mortality depending on whether blood was transfused and, if so, how much. RESULTS: Dukes' stage (p < 0.001), rectal tumours (p < 0.05) and the number of units transfused (p < 0.05) were significantly associated with cancer related mortality. Patients with rectal cancer transfused with 1-2 units had significantly better survival than those transfused with more than 4 units (p < 0.05), but this was not the case for colonic tumours. There was no significant association between blood transfusion and the incidence of infective complications. CONCLUSION: Though there seems to be an association between the number of units of blood transfused and cancer related survival in patients with rectal cancer, this does not necessarily imply causation. We recommend that until this is clarified by large, prospective investigations, autologous blood should be used whenever possible, and unnecessary blood transfusion should be avoided.

Adenocarcinoma↗

Trunk muscle strength and back muscle endurance in construction workers with and without low back disorders.

The aim of this study was to test the hypothesis that male workers exposed to heavy work and with no lifetime history of a low back disorder (group A) have better trunk muscle strength and back muscle endurance compared to male workers with the same work exposure but with a probable (group B) or definite low back disorder (group C). Group A (n = 42) was clinically negative on physical examination. Group B (n = 75) was clinically negative or uncertain and group C (n = 86) was clinically positive, with current or previous low back disorders occurring in both groups. Group A had a significantly higher mean intraindividual extension/flexion ratio, namely 1.29 versus 1.19, in group C. The mean values for maximum isometric trunk extension and flexion strength did not differ between the groups. The isometric trunk extensor endurance was significantly lower in group C than in both group A and group B.

Adult↗

Relationship between testicular measurements, body weight and semen quality in young dairy bulls.

Dairy bulls, 322 Ayrshires (Ay) and 85 Friesians (Fr), were studied at the age of 11 months. Of the bulls, 286 Ay-bulls and 80 Fr-bulls produced semen of acceptable quality for use in A.I. Scrotal circumference, tonometer measure, scrotal fold thickness, 1-year body weight and testicular palpation were used to predict unsuitable bulls for A.I. Non-return rate was used as a measure of fertility. Scrotal fold thickness and 1-year weight had no significant correlation with fertility or semen quality. Scrotal circumference had a significant positive correlation with fertility. Tonometer ratio had a significant negative correlation with fertility. Testicular palpation was the best basis for predicting bulls with poor semen quality in this study. Twelve bulls were recorded as having testicles of different sizes, 1 testicle being more than 20% bigger than the other. Only 2 of these 12 bulls produced semen of acceptable quality. One of these 2 bulls was, after slaughter, diagnosed as having a hereditary testicle disease. Friesians were shown to have significantly higher fertility than Ayshires.

Animals↗

Computerized and subjective assessments of post-thaw motility of semen from Finnish Ayrshire AI bulls in relation to non-return rates.

A semen analyser (Lazymot), was used to evaluate post-thaw motilities in 296 batches of semen from 74 Ayrshire bulls used for artificial insemination (AI). Motility was also assessed subjectively. A significant correlation was observed between assessments of motility using the Lazymot analyser and the subjective assessments. There was no correlation between post-thaw motility assessments and non-return rates in relation to the batches examined, which met Finnish criteria for use in AI. This suggests that criteria for post-thaw semen motility should not be increased beyond the present requirement for 40% motile spermatozoa.

Animals↗

Incidence of new primary cancers after adjuvant tamoxifen therapy and radiotherapy for early breast cancer.

The incidence of new primary cancers was evaluated in 3538 postmenopausal patients who had received surgical treatment for primary breast cancer. Of these patients, 1828 with a low risk of recurrence received no further treatment. High-risk patients were randomly assigned to one of two groups. The first group (n = 846) received postoperative radiotherapy, while the second group (n = 864) received radiotherapy plus tamoxifen at a dose of 30 mg given daily for 48 weeks. The median observation time was 7.9 years. In comparison with the number of new cancers in the general population, the number of new cancers in the three groups was elevated mostly due to a high number of cancers of the contralateral breast and of colorectal cancers in the high-risk groups. The cumulative risk of nonlymphatic leukemia was increased among patients who received postoperative radiotherapy (P = .04). Cancer incidence in the high-risk tamoxifen-treated group relative to that in the high-risk group not treated with tamoxifen was not significant (1.3). No protective effect of tamoxifen on the opposite breast was seen (rate ratio for breast cancer = 1.1), but a tendency to an elevated risk of endometrial cancer was observed (rate ratio = 3.3; 95% confidence interval = 0.6-32.4). Continued and careful follow-up of women treated with tamoxifen is necessary to clarify the potential cancer-suppressive or cancer-promoting effects of this drug.

Aged↗

Identification of three amino acids in the platelet-derived growth factor (PDGF) B-chain that are important for binding to the PDGF beta-receptor.

Platelet-derived growth factor (PDGF) is a disulfide-linked dimeric protein composed of two homologous polypeptide chains denoted A and B. Two types of PDGF receptors, alpha and beta, have been characterized. Whereas PDGF-AA binds only to PDGF alpha-receptors, PDGF-BB binds to both receptor types with high affinity. To map the regions of the PDGF B-chain that confer its ability to bind with high affinity to the PDGF beta-receptor, we expressed PDGF A/B-chain chimeras in COS cells and analyzed them with regard to PDGF alpha- and beta-receptor binding. A systematic analysis revealed that replacement of Asn-115, Arg-154, and Ile-158 of the PDGF B-chain with the corresponding A-chain amino acids led to a dramatic decrease in the affinity for the beta-receptor. Conversely, introduction of B-chain amino acids into the A-chain in the region spanning from Asn-115 to Ile-158 yielded a product with high affinity for the beta-receptor. These data thus indicate that Asn-115, Arg-154, and Ile-158 are likely to be part of the active site of the PDGF B-chain.

Amino Acid Sequence↗

The preparation of biotinyl-epsilon-aminocaproylated forms of the vasoactive intestinal polypeptide (VIP) as probes for the VIP receptor.

Vasoactive intestinal polypeptide (VIP) was biotinyl-epsilon-aminocaproylated using sulfosuccinimidyl-6-(biotinamido) hexanoate thereby producing a series of products that were separated by high performance liquid chromatography (HPLC). Seven VIP-derivatives were isolated and the number and location of biotinyl-epsilon-aminocaproylation was determined by a combination of enzymatic degradation and plasma desorption mass spectrometry (PDMS). Receptor binding experiments with the VIP biotinyl-epsilon-aminocaproylated derivatives revealed IC50 values for the monobiotinyl-epsilon-aminocaproylated peptides that were 1.3-3.2 times higher than for natural VIP. All isolated biotinyl-epsilon-aminocaproylated derivatives possess VIP-like bioactivity as shown by an assay measuring pancreatic juice secretion in cat, VIP biotinyl-epsilon-aminocaproylated in position lysine being almost equipotent with natural VIP.

Amino Acid Sequence↗

Inhibition of complement components C3 and C4 by cadralazine and its active metabolite.

The effect of cadralazine and its active metabolite CGP 22639 on the covalent binding reaction of C4 and C3 has been studied. Trypsin-Sepharose was used to activate radio-labelled C3 and C4 and binding of the radio-labelled protein to the trypsin-Sepharose was measured. Cadralazine inhibited 50% of the binding of C3 and C4 at concentrations of 19 mmol/l and 15 mmol/l, respectively. Its active metabolite was more potent and inhibited 50% of the C3 and C4 binding at concentrations of 8 and 3.5 mmol/l, respectively. These concentrations are much higher than those found in plasma during therapy. This is consistent with the clinical observation that in patients with normal kidney function cadralazine is not an inducer of SLE.

Antihypertensive Agents↗

Nursing home care: factors influencing the quality of life in a restricted life situation.

The quality of life and care situation of 191 patients living in 4 nursing homes (NHs) were evaluated with regard to patient functional impairment and staff competence. Patient disability levels in the different NHs were similar. A high incidence of dementia in combination with somatic diseases were limitations to achieve quality of life. The patients had limited access to privacy. Their possibilities to communicate with the world outside, interpersonally, and via mass-media were small. Only about half of them went out of the NHs during their mean stay of 1.8 years, but they were often visited by relatives and friends. The staff seemed to be indifferent to the patients' needs, which was reflected in insufficient physical and mental training, bad mealtime routines and only a minute of time allowed for personal acquaintance at admittance. The competence of the nursing staff and their working in a nursing team seemed to be of major importance in the care situation for the quality of life available. It was evident that there was a great need to improve the care situation.

Activities of Daily Living↗