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Biomedical subjects

O Andersson

Publications and source records attributed to O Andersson.

At least 19 recordsLinked to original sources

On laboratory problems in diagnosing mild von Willebrand's disease.

By providing some examples of variations in the levels of von Willebrand factor antigen (vWF:Ag), ristocetin cofactor, and Factor VIII during one month, the authors wish to emphasize the difficulty of diagnosing mild forms of von Willebrand's disease (vWD), especially type I. In three of 15 normal female volunteers the vWF:Ag levels, on some sampling occasions, were so low (0.25-0.30 IU/mL, normal greater than 0.50 IU/mL) that the diagnosis of vWD type I might be made while on other occasions normal levels were obtained. The coefficients of variation (CV) for vWF:Ag in these three women were 12%, 25%, and 43%. However, CVs of similar magnitude were also observed for "non-diseased" males and females. The ratio F VIII/vWF:Ag also varied greatly. In the three women with suspected vWD it was 36%, 15%, and 34%. A representative level for the entire cycle of vWF:Ag and ristocetin cofactor seems to have been obtained in the follicular phase and therefore it is suggested that in order to make the diagnosis of vWD type I, at least in females, blood samples should be taken in this phase.

Adult

Rat lung polycholorinated biphenyl-binding protein: effect of glucocorticoids on the expression of the Clara cell-specific protein during fetal development.

Certain metabolites of polychlorinated biphenyls (PCBs) are retained in the Clara cells and in the airway lumen of rodent lung due to their interaction with a secretory 13-kDa protein. The expression of this Clara cell-specific, PCB-binding protein (PCB-BP) during the fetal development of the rat lung was studied by means of ligand binding and a monospecific antiserum. The PCB-BP and specific 4,4'-bis([3H]methylsulfony)-2,2',5,5'-tetrachlorobiphenyl binding was first detected on gestational Day 19 and subsequently the levels of PCB-BP and specific ligand binding increased as a function of gestational age. The start site of transcription for the rat PCB-BP gene was determined by primer extension analysis and the information thus obtained was used to develop a quantitative assay for the corresponding mRNA based on solution hybridization and S1 nuclease mapping. The appearance of PCB-BP mRNA during fetal lung development preceded the detection of immunoreactive protein and ligand binding by 1 day. By Day 21, the level of PCB-BP mRNA was 15 ng/100 micrograms total lung RNA which is approximately 30-40% of adult levels. In utero exposure to the synthetic glucocorticoid betamethasone was shown to increase specific 4,4'-bis([3H]methylsulfonyl)2,2',5,5'- tetrachlorobiphenyl binding, PCB-BP protein, and PCB-BP mRNA if administered from gestational Day 18 and onward. By Days 21-22, glucocorticoid treatment resulted in a two- to threefold increase in the levels of specific ligand binding, immunoreactivity, and mRNA, i.e., to approximately adult levels.

Animals

Bronchial exudation of bulk plasma at allergen challenge in allergic asthma.

This study examined plasma exudation into the bronchial lumen after allergen challenge. A novel low-trauma technique was developed to challenge and lavage a medium-sized lingular or middle lobe bronchus. Eleven subjects with challenge-assessed pollen-sensitive asthma were allocated to fiberbronchoscopy in the supine position. In the control bronchus 0.5 ml diluent was instilled. The bronchus was occluded proximally 3 min later by inflation of a balloon, and lavage was carried out twice with 25 ml saline. Incremental doses of allergen solution (0.5 ml) were then instilled in the contralateral lung. The challenge continued until a clearly visible bronchial reaction occurred and was immediately followed by the same lavage as on the control side. The lavage liquids were analyzed for the presence of plasma exudation and mast cell activation indices. On the allergen-challenged side, tryptase, reflecting mast cell activation, was increased by 150% (p < 0.01) compared with the control side. Fibrinogen (mol wt 340,000), reflecting large protein exudation, was increased by 840% (p < 0.05), and N-alpha-tosyl-L-arginine-methyl esterase activity, reflecting both large protein exudation and mast cell activation, increased by 480% (p < 0.01). The level of albumin (mol wt 69,000), the major luminal protein under baseline conditions, increased but not significantly. We conclude that activation of mast cells and luminal entry of little sieved plasma exudates occur early after endobronchial allergen provocation in human subjects with allergic asthma.

Albumins

The interconnection between sympathetics, microcirculation, and insulin resistance in hypertension.

The pathophysiology of the frequent association of insulin resistance and hypertension has not been elucidated. The skeletal muscle is the major site of insulin resistance; when stimulated with insulin, the hypertensive skeletal muscles extract less glucose than the normotensive. We postulate that hypertension-related changes in the skeletal muscle microcirculation contribute to the impaired glucose uptake in hypertension. Vascular rarefaction in hypertension impairs the delivery of insulin and glucose to muscle cells. Insulin resistance has been described both in human and experimental hypertension and both conditions are associated with vascular rarefaction. Functional studies (response to whole body or forearm exercise) and anatomic investigations (conjunctival photography, mesenteric and muscle biopsies) show vascular rarefaction in human hypertension. In addition, patients with hypertension are known to have a larger proportion of insulin resistant, poorly vascularized fast twitch muscle fibers. A few interventions can increase or decrease insulin resistance and these effects can be explained on hemodynamic grounds. Beta adrenergic blocking agents aggravate insulin resistance, and their main hemodynamic effect is a decrease of cardiac output. Converting enzyme inhibitors, alpha adrenergic blocking agents and possibly calcium antagonists decrease the insulin resistance, and their major hemodynamic effect is vasodilation. Physical training decreases insulin resistance; a higher capillary density in skeletal muscles is the hallmark of physical training. A hypothesis ought to rest on sufficient supporting data and its validity ought to lend itself to experimental verification. We believe our hypothesis meets both criteria. After outlining the supporting evidence we propose a number of tests to prove or disprove the hypothesis. In addition to the testable hypothesis we also speculate on the possible cause of the frequent association between hypertension and insulin resistance. We propose that both insulin resistance and blood pressure elevation represent a facet of the "defense reaction" which might have offered an early survival advantage and may, over evolutionary times, have fostered natural selection of subjects with both conditions.

Animals

Purification and level of expression in bronchoalveolar lavage of a human polychlorinated biphenyl (PCB)-binding protein: evidence for a structural and functional kinship to the multihormonally regulated protein uteroglobin.

A human lung polychlorinated biphenyl (PCB)-binding protein was purified by sequential chromatography of lavage fluid incubated with the tritium-labeled, high-affinity ligand, 4,4'-bis(methylsulfonyl)-2,2',5,5'-tetrachlorobiphenyl. From sodium dodecyl sulfate polyacrylamide gel electrophoresis gradient gels, it was evident that a single band with an approximate molecular weight of 13 kD was present in the eluate from the final chromatographic step. Antibodies raised against the human lung PCB-binding protein detected a single band of corresponding size in lavage fluid in immunoblotting experiments. Furthermore, the antibodies detected significantly higher levels of the lung PCB-binding protein in lavage fluid from nonsmokers as compared to smokers. The purified protein was sequenced, and an alignment of the obtained aminoterminal amino acid residues of the human lung PCB-binding protein to uteroglobin and to a rat lung PCB-binding protein revealed an overall positional identity of approximately 45%. The amino acids suggested to participate in ligand binding of uteroglobin were extensively conserved in the PCB-binding proteins. Thus, we conclude that we have purified and raised antibodies against a human lung PCB-binding protein and that it has a structural as well as a functional kinship to the steroid-binding and multihormonally regulated rabbit protein uteroglobin.

Amino Acid Sequence

Glucocorticoid receptor mRNA expression in pulmonary alveolar macrophages in sarcoidosis.

The presence of the glucocorticoid receptor was demonstrated by immunocytochemistry in pulmonary alveolar macrophages obtained by bronchoalveolar lavage. Also, GR mRNA content was determined by solution hybridization in PAM from 12 healthy volunteers and in 6 patients with sarcoidosis. No significant differences with regard to GR mRNA expression was detected between the two groups examined. For comparison, lung tissue from three patients undergoing thoracic surgery was examined and found to contain GR mRNA levels in the same range. As an indication of GR function, we also determined the mRNA levels of a glucocorticoid-regulated gene, metallothionein IIA, during basal conditions and after in vitro incubation of PAM with dexamethasone. Neither the control sample nor the dexamethasone-stimulated MTII mRNA values in PAMs differed significantly between the two groups. Solution hybridization is a rapid, sensitive and convenient assay which enables accurate and specific quantitation of GR mRNA in PAM. The GR mRNA content and basal as well as dexamethasone-induced MTII mRNA levels in PAM from patients with sarcoidosis is not significantly different from those in healthy volunteers.

Adult

Cloning, structure, and expression of a rat binding protein for polychlorinated biphenyls. Homology to the hormonally regulated progesterone-binding protein uteroglobin.

Certain metabolites of polychlorinated biphenyls (PCBs) are retained in the Clara cells and in the airway lumen of rodent lung due to their interaction with a secretory 13-kDa protein. Here, we report the isolation of a cDNA encoding the rat lung PCB-binding protein. The identity of the PCB-binding protein is supported by expression of the cDNA in Cos-1 cells where the homogenates from transfected cells show specific binding of 4,4'-bis([ 3H]methylsulfonyl)-2,2',5,5'-tetrachlorobiphenyl, a high affinity ligand for the PCB-binding protein. Also a monospecific antiserum to the PCB-binding protein recognizes a 13-kDa protein in the homogenates of transfected cells but not in the corresponding fraction of mock-transfected cells. Northern blot analysis of total RNA from different rat tissues demonstrates that the cDNA detects a approximately 600-base pair mRNA which appears to be solely expressed in lung. Interestingly, DNA sequence analysis and prediction of the amino acid sequence reveals that the PCB-binding protein shares 53% positional amino acid identity with uteroglobin, a progesterone-binding protein found in rabbit uterus and lung. Furthermore, amino acids shown by x-ray crystallography to delineate the central cavity of uteroglobin, which fits progesterone, are highly conserved in the two proteins.

Amino Acid Sequence

Influences of maternal smoking and fetal sex on maternal serum oestriol, prolactin, hCG, and hPI levels.

A total of 222 pregnant women had repeated hormone assays between 20 weeks and delivery; 86 of the women were smokers. The maternal hormone balance appeared to be affected by smoking. Smoking affected maternal serum levels of hPL and hCG in pregnancies with a female fetus whereas maternal serum concentrations of oestriol and prolactin were affected in pregnancies with a male fetus. Significantly higher hCG levels were found in mothers who smoked and had a girl than in those who smoked and had a boy. On the basis of our results we feel that smoking mainly affects the placenta.

Adult

Acute and long-term antihypertensive effect of bopindolol once daily or once weekly.

Fourteen male patients, mean age 53 years (range 35-64), were included in an initial 3 months' double-blind crossover study, in which 1-2 mg bopindolol, a nonselective beta blocker with intrinsic sympathomimetic activity (ISA), was compared with 100-200 mg metoprolol regarding effects on blood pressure and heart rate. During the subsequent long-term therapy, eight patients were trained to measure home blood pressure, and in these patients bopindolol 1 mg daily was compared to 8 mg once weekly in a double-blind fashion for 3 weeks on each regimen. Bopindolol (mean dose 1.35 mg/day) caused a significant blood pressure reduction, 26/15 mm Hg, as did metoprolol, 24/3 mm Hg (mean dose 144 mg/day) (NS). Supine and standing heart rates were reduced during both bopindolol and metoprolol treatment. During long-term therapy with bopindolol satisfactory blood pressure control was achieved for 1 year in 11 patients. Heart rate was significantly reduced after 2-3 months' treatment and during the entire 1-year follow-up. Few and well-tolerated side effects were reported. During treatment with bopindolol 8 mg once weekly, the blood pressure control was maintained satisfactorily over the week and no significant differences were observed in comparison with daily administration (1 mg) of the drug.

Adrenergic beta-Antagonists

Effect of treatment of hypertension in the primary preventive trial, Göteborg, Sweden.

1 A treatment group comprising 635 hypertensive men (casual SBP greater than 175 or DBP greater than 115 twice) was compared with a reference group (n = 391 men; casual SBP greater than 175 or DBP greater than 115 only at screening). All men belonged to the same population sample of 7,455 men aged 47-54 yr. 2 The two groups did not differ with respect to age, smoking habits or cholesterol values, but screening BPs were higher in the treatment group. 3 During 4.3 years' follow-up there was a significantly lower total death rate in the treatment group compared with reference group. 4 There was also a strong tendency towards lower incidence of non-fatal myocardial infarction (P = 0.06). The pooled incidence of non-fatal myocardial infarction and fatal CHD was lower in the treatment group than in the reference group (P less than 0.03).

Adrenergic beta-Antagonists

Tienilic acid in mild to moderate hypertension.

Tienilic acid has blood pressure lowering properties alone and in combined treatment with beta-adrenergic blocking agents; 250 mg of tienilic acid seems to correspond to 50 mg of hydrochlorothiazide. Tienilic acid effectively reduces serum urate and has no marked or rapid effect on potassium balance. During short-term treatment, no impairment of glucose tolerance was found.

Adrenergic beta-Antagonists

Blood pressure reduction and vascular adaptation. A study on long-term effects of treatment with mefruside or atenolol.

Systemic BP reduction, calf blood flow and vascular resistance in the calf were determined in forty-two previously untreated patients with mild to moderate essential hypertension (WHO I-WHO II) before and after 6 weeks, 6 months and 18 months of BP-lowering treatment with mefruside (25 mg daily) or atenolol (100--400 mg daily). Blood flow was determined with venous occlusion plethysmography using a mercury-in-rubber strain gauge technique in the supine patient. Auscultatory BP was measured on the right arm simultaneously with the flow determinations and resistance was calculated from the flow and pressure. BP was reduced significantly and to the same extent by the two drugs. In the atenolol group a rise in resting resistance and a corresponding fall in resting blood flow was seen initially. These changes were entirely normalized during continued treatment for 18 months. In the mefruside group no significant haemodynamic changes during treatment were observed at rest apart from the BP fall. None of the drugs reduced resistance at "maximal" vasodilatation, indicating that no regress of the hypertensive structural changes of the calf blood vessels had taken place.

Adult

Heart and kidney involvement and prognosis in hypertension. A study concerning referred hypertensive patients and hypertensive patients found by blood pressure screening.

Severity of hypertension, frequency of secondary hypertension and prognosis have been compared in two groups of hypertensive men. The first group (n=686) was taken from a blood pressure screening of a total population sample. The other group (n=154) consisted of hypertensive men, referred to a hypertension clinic by physicians. The mean age of the groups was the same, (X=52 years, range 46--59 years). All went through the same investigations and were followed up and treated in a similar way at the hypertension clinic. The referred men had more severe hypertension, as shown by significantly more heart and kidney involvements. They also had a higher incidence of myocardial infarction, implying a poorer prognosis with regard to cardiovascular disease. The analysis shows the importance of a detailed description of studied groups, not only in terms of blood pressure, age and sex, but also with respect to the frequency and degree of present and previous signs of heart and kidney involvement. With such a description it is possible to compare results from different studies regarding pathophysiological mechanisms and the effect of treatment in hypertension.

Cerebrovascular Disorders