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Biomedical subjects

B A Jensen

Publications and source records attributed to B A Jensen.

At least 37 records · Page 2Linked to original sources

Antibody response to whole cells and teichoic acid of Staphylococcus aureus strain E 1369 in human sera.

A whole cell Staphylococcus aureus enzyme-linked immunosorbent assay (ELISA) using the protein A-deficient strain E 1369 as antigen was compared to an ELISA with cell-wall teichoic acid, extracted from the same strain, as antigen for the detection of IgG antibodies against S. aureus in human sera. A total of 178 serum samples from 119 patients with S. aureus endocarditis, complicated and uncomplicated septicaemia, non-S. aureus endocarditis and septicaemia were investigated together with sera from 155 healthy controls. The sensitivity in diagnosing S. aureus endocarditis was better for the whole cell-ELISA (83%) as compared to the teichoic acid-ELISA (61%), and the same was true for complicated septicaemia (41% vs 29%). The whole cell ELISA was also more specific for S. aureus infections with only 3.6% false positive test values compared to 7.1% for the teichoic acid-ELISA. The differences were however, not statistically significant. None of the assays were able to distinguish between complicated and uncomplicated S. aureus septicaemia.

Antigens, Bacterial↗

Plasma fibronectin concentration in normal pregnancy and pre-eclampsia.

Plasma fibronectin concentration was determined by electroimmunoassay in 111 normal pregnant women and in 23 pregnant with evidence of pre-eclampsia. The plasma fibronectin concentration during the period of normal pregnancy showed a significant increase. In mild or severe pre-eclampsia patients, the plasma fibronectin concentration was significantly higher than that measured at normal 38-41 weeks of gestation. The present findings suggest that measurement of plasma fibronectin might be of diagnostic value in pre-eclampsia.

Adolescent↗

Plasma tetranectin in healthy male and female individuals, measured by enzyme-linked immunosorbent assay.

Tetranectin is a novel protein recently isolated from human plasma. It is a tetramer, composed of four identical, non-covalently bound, 181-amino-acid polypeptide chains (Mr = 20,100). We report here the quantification of plasma tetranectin in 457 healthy individuals, aged from birth to 85 years, using a newly developed sensitive and reproducible enzyme-linked immunosorbent assay (ELISA). Tetranectin was demonstrable in all subjects investigated, and within each sex and defined age group the concentration was well controlled within a relatively narrow range. The mean plasma tetranectin level in newborn infants (cord plasma) was about 8 mg/L. This was significantly less than in later life, during which mean plasma tetranectin level varied between 10 and 12 mg/L. After the age of 9 years, tetranectin level was continuously higher in males than in females, but the variations through the span of life were almost identical. Thus, a transitory increase in plasma tetranectin was observed in early puberty, reaching its climax about the age of 11 to 12 in girls and 14 to 15 in boys. A quantitatively similar, additional peak was observed during the period of 50 to 59 years of age in both sexes, whereupon the tetranectin concentration gradually decreased. The biologic function of tetranectin remains to be elucidated. Recently, we have reported that tetranectin is contained within hepatocytes and various endocrine cells, all known to process peptide hormones or glucoproteins. We propose that tetranectin may be involved in intracellular and extracellular serine protease-mediated proteolysis.

Adolescent↗

Immune-induced dermal connective tissue alterations in rabbits chronically immunized with bovine serum albumin: biochemical studies on collagen, glycosaminoglycans, RNA, and DNA.

Rabbits were chronically immunized by repeated intravenous injections of bovine serum albumin and compared to saline injected controls. All sensitized animals developed antibodies to albumin, but in only a few were circulating immune complexes detected. The dermal biosynthesis of dermatan and heparan sulfate in vivo was significantly restrained following immunization due to a reduced cellular synthesis. The collagen type III/I ratio was significantly repressed in the skin of immunized rabbits, in particular in the acid soluble collagen fraction containing newly formed collagen. Further, the hydroxyproline/DNA ratio, expressing the collagen accumulation per cell, was increased, indicating that the secretion of collagen type I was enhanced. These alterations in the formation and accumulation of matrix components were not correlated to the occurrence of circulating immune complexes or the antibody response. Thus, compared to previous investigations on vascular connective tissue, persistent immunostimulation may alter connective tissue metabolism systemically, and it appears that the metabolism of matrix components characteristic of early connective tissue formation and inflammation is particularly susceptible. These observations may be of significance as regards systemic involvement and chronicity in various inflammatory connective tissue diseases.

Animals↗

Immune-induced vascular connective tissue alterations in rabbits chronically immunized with bovine serum albumin: biochemical studies on collagen, glycosaminoglycans, RNA, and DNA in normal and injured aorta.

Repeated intravenous injections of bovine serum albumin in rabbits caused a significant reduction in the aortic in vivo biosynthesis of chondroitin-4,6-sulfate, whereas no changes were observed in the synthesis of other glycosaminoglycans nor in the content of collagen. This contrasts the biochemical changes generally seen in acute vascular injury. When experimentally elicited vascular injury and repair processes were induced in chronically immunized rabbits, the proliferative response was greatly inhibited, as reflected by a significant diminution of the DNA amount. Also, the vascular connective tissue matrix repair was restrained: the aortic content of collagen and the collagen type III/I ratio was repressed, and the in vivo biosynthesis of sulfated glycosaminoglycans was markedly reduced. All immunized rabbits developed antibodies to bovine albumin, but in only a few were circulating immune complexes detected. The inhibitory effect of persistent immunostimulation on the nonspecific processes of repair in vascular connective tissue may be of significance as to chronicity of vasculitis, as well as inflammation and repair in general, in inflammatory connective tissue diseases.

Animals↗

Collagen type III predominance in newborns with congenital dislocation of the hip.

The collagen content and the relative distribution of collagen Types I and III were measured in umbilical cords from newborns with congenital dislocation of the hip (CDH) and healthy controls. The total content of collagen per mg dry tissue tended to be reduced. In newborns with CDH the collagen III/I ratio was higher than in the controls. If generalized, these alterations in collagen metabolism may explain the joint hypermobility seen in CDH. It is suggested that the redistribution of collagen Types III and I during normal fetal development and early infancy may be delayed in CDH.

Collagen↗

Circulating monoclonal IgM lambda cryoglobulin with collagen type I affinity in vasculitis.

A previously fit 66-years-old male primarily presented symptoms compatible with Henock-Schönlein's purpura, from which he seemingly recovered. Shortly hereafter he relapsed with an IgM lambda essential monoclonal cryoglobulinemia type I, presenting a systemic, necrotizing vasculitis, with low titer of circulating immune complexes and complement consumption. Glucocorticoid treatment and plasmapheresis did not prevent an ultimately lethal course. An indirect immunoperoxidase technique showed that the cryo-IgM bound to the interstitial connective tissue corresponding to the localization of collagen type I. In addition it bound to affinity purified human procollagen type I. These results indicate, that the IgM lambda of the proband was an autoantibody with collagen type I specificity.

Aged↗

Identification and quantification of a monoclonal IgM euglobulin: pitfalls and methodologic instruction.

In a patient with Waldenström's macroglobulinemia routine agarose gel electrophoresis and immunofixation disclosed an IgM-kappa M-component with beta-mobility, but failed to unveil a major monoclonal IgM-kappa euglobulin. This, however, was demonstrated when the procedures were performed in a buffer with NaCl-ion-strength of 0.1 M. Similarly, IgM quantification by routine nephelometry and electroimmunoassay led to dramatically inconsistent results. By a simple agarose gel electrophoresis in NaCl 0.1 M the IgM euglobulin was quantified proportional to the serum concentration of albumin. The identification and classification of an M-component, being exceedingly important diagnostically, may be missed, when solely routine electrophoresis and immunofixation is employed. As regards the quantification of M-components, these are not merely pathologic immunoglobulins nosologically. Also, biochemically they differ from normal, polyclonal immunoglobulins, resulting in immunological techniques being inapplicable for their quantification. For quantitative purposes, a simple, comparative agarose gel electrophoresis is described.

Aged↗

Immune-induced vascular connective tissue alterations in rabbits chronically immunized with bovine serum albumin: morphological and morphometric studies on normal and injured thoracic aorta.

The effect of persistent immunostimulation on normal and mechanically injured thoracic aorta was investigated histologically, histochemically and morphometrically. In the uninjured vessel wall no alterations suggestive of acute inflammation were observed following immunization, in accordance with previous biochemical studies. When mechanically elicited vascular injury and repair processes were induced in chronic immunostimulated rabbits, the neo-intimal aortic smooth muscle cell nuclear volume fraction of the vessel wall was significantly repressed, indicating, that the proliferative response to injury was inhibited. Further, the neo-intimal volume fraction of the vessel wall was reduced, suggesting impaired matrix neoformation. A highly significant linear correlation existed between the biochemically estimated DNA concentration and the nuclear volume fraction of smooth muscle cells in the vessel wall (r = 0.6275, P = 5 X 10(-5). Thus, the present study confirms previous biochemical observations, that the early processes of vascular inflammation and repair, i.e. smooth muscle cell proliferation and matrix accumulation, is inhibited following persistent immunostimulation. In addition to describing the histological correlates to the biochemical findings, important regional differences were quantified.

Animals↗

Effect of D-penicillamine on the mechanical properties of aorta, muscle tendon and skin in rats.

The biomechanical properties of rat aorta, muscle tendon and skin were studied after daily D-penicillamine treatment (500 mg/kg) for 5, 10 and 42 days. D-Penicillamine treatment for 5 days resulted in increased aortic extensibility. After long-term treatment the aorta exhibited a shift towards decreased extensibility and increased stiffness at small 'stress' values. Simultaneously the dry weight and diameter of the aortic samples were increased after D-penicillamine treatment for 42 days. After correction of the mechanical parameters for the increased amount of tissue of the samples, the stiffness at small 'stress' values was still increased and the mechanical stability at high 'stress' values retained. This is in contrast to the marked reduction in the strength of muscle tendon and skin of the same animals after D-penicillamine treatment for 42 days. This study demonstrates that a primary increase in the extensibility of aorta may elicit a reactive formation of vascular connective tissue. It is proposed that aortic smooth muscle cells are activated by an increased pulsatile distension of the vessel wall secondary to the early effect of D-penicillamine on collagen and elastin. The resulting excess deposition of collagen and elastin leads to increased stiffness, which may in turn increase the susceptibility of the aortic wall to hemodynamic injury. Consequently D-penicillamine may not as proposed counteract the development of atherosclerosis.

Animals↗

Plasma fibronectin concentrations in patients with severe burn injury.

Plasma fibronectin concentrations were measured in 33 patients with major burn injury. Changes in plasma fibronectin concentration were related to the day of burn injury, surgery and to the development of sepsis. Within 24 hours of the burn injury and surgical treatment, a decrease of the plasma fibronectin concentration was observed, which returned to normal values within 72 hours. A decrease in the plasma fibronectin concentration was observed as sepsis developed, while recovery from septicaemia was associated with plasma fibronectin concentration returning to normal values.

Adolescent↗

Demonstration of fibronectin in normal and injured aorta by an indirect immunoperoxidase technique.

The presence and localization of fibronectin in normal and mechanically injured aorta in rabbits was studied using an indirect immunoperoxidase technique on tissue specimens fixed in formaldehyde, embedded in paraffin and pretreated with pepsin. The effect on staining quality of treatment with testicular hyaluronidase prior to immunoperoxidase staining was also examined. In the intima from normal aorta fibronectin was present in the subendothelial basal layer, along the internal and external elastic laminae, around and between the smooth muscle cells of the media and along the collagen and elastic fibres in the adventitia. Sixteen days after a single mechanical dilatation of the descending thoracic aorta all animals developed gross atherosclerotic-like changes. Microscopic examination revealed prominent neo-intimal hyperplasia with subendothelial, cushion-like thickenings but no medial or adventitial alterations. Fibronectin, in increased amounts, was found between and around the endothelial cells and in the subendothelial thickenings between the proliferating smooth muscle cells in relation to the fine, thin elastic and argyrophilic fibres. In the media and adventitia the amount and distribution of fibronectin was indistinguishable from uninjured control aortas. Treatment with testicular hyaluronidase before immunoperoxidase staining resulted in a higher staining resolution in normal and injured aorta. The conspicuous observation in the present study is that fibronectin exclusively accumulates in areas of tissue repair. The origins and functions of fibronectin during tissue injury and repair are discussed.

Animals↗

The association of affective disorder with Huntington's disease in a case series and in families.

Major affective disorder clinically similar to the disorder found in conditions other than Huntington's Disease (HD) was found in 41% of patients with HD in a consecutive case series ascertained through multiple sources in a defined geographical area. The association appears to be confined to certain families, and affective disorder may appear as long as 20 years before the onset of chorea and dementia. The association may represent genetic heterogeneity in HD.

Adolescent↗

Conduct disorder and affective disorder among the offspring of patients with Huntington's disease.

The rate of occurrence of conduct disorder and affective illness was studied for a sample of 112 offspring of 34 Huntington's Disease (HD) patients. Psychiatric disorder in the offspring was assessed as a function of: (1) age of the parent at the onset of symptoms of HD; (2) family disorganization; and (3) psychiatric disorder in either parent. The findings indicated an increased frequency of conduct disorder in disrupted families, most especially in those where the HD parent had an early onset of symptoms and the non-HD parent showed psychiatric disorder. Affective disorder in the offspring was most strongly associated with the presence of similar symptoms in the HD parent. Affective disorder, but not conduct disorder, may be an early manifestation of the HD gene. The implication of these findings for genetic counselling is discussed.

Adolescent↗

Abnormal ocular motor control in Huntington's disease.

We studied eye movements in 50 patients with Huntington's disease. Fixation was impaired in 73% of patients; such individuals had difficulty in suppressing saccades toward novel visual stimuli. Impaired initiation of saccades was manifest by increased reaction time (89%) and inability to make a saccade without head movement (89%) or blink (35%). Saccades and quick phases of nystagmus were slowed in 62%. Smooth pursuit was abnormal in 60%, and vergence in 33%. The vestibulo-ocular reflex and the ability to hold eccentric gaze were preserved even late in the disease.

Adult↗

D-penicillamine-induced angiopathy in rats. The effect of high dose D-penicillamine treatment on aortic permeability to albumin and on the ultrastructure of the vessel.

Male Sprague-Dawley rats were treated with D-penicillamine (D-pen) 500 mg/kg/day for 10 or 42 days. Pair fed rats served as controls. Changes in aortic morphology were examined by light- and transmission-electron microscopy (TEM). In addition, the endothelial permeability and the penetration through the aortic wall of albumin were studied 10 minutes, 24 and 48 hours after i. v. injection of human serum 131I-albumin (131I-HSA). TEM revealed extensive elastolysis in the arterial wall of D-pen-treated rats, consistent with an inhibitory effect on crosslink formation. In experimental animals excess deposition of collagen and glycoaminoglycans was observed in the subendothelial and medial layer of the aortic wall, together with prominent basal membrane substance around aortic smooth muscle cells. The aorta/serum-ratio and the radioactive build-up 24 and 48 hours after injection of 131I-HSA was reduced in animals treated with D-pen for 42 days, indicating an impeded transmural transport of tracer which may be caused by a steric exclusion effect of abundant hyaluronate. The endothelial ultrastructure was unaffected by D-pen, and no differences in aortic 131I-HSA radioactivity or aorta/serum-ratio were recorded between experimental and control groups 10 minutes after tracer injection, indicating that the permeability of the endothelial barrier to albumin remained unaffected by D-pen treatment. These observations support the hypothesis that treatment with high doses of D-pen may induce a fibroproliferative response in rat aorta, possibly by an inhibitory effect on the cross-linking of collagen and elastin.

Animals↗

D-penicillamine-induced angiopathy in rats. Changes in aortic collagen, glycosaminoglycans, DNA and RNA in rats treated with D-penicillamine.

Male Sprague-Dawley rats were treated with D-penicillamine (D-pen) in doses of 100, 250 or 500 mg/kg per day for 10, 32, 42 or 70 days. In addition animals were examined 28 days after withdrawal from 42 day's treatment with D-pen at 100 or 500 mg/kg per day. Pair-fed rats served as controls. The changes in aortic collagen, glycosaminoglycans (GAGs), DNA and RNA were studied. D-Pen had a dose- and time-related solubilizing effect on aortic collagen, which regained normal resistance to extraction within 28 days after cessation of the treatment. In contrast, D-pen caused a progressive accumulation of hydroxyproline (Hyp) in the aortic wall during and after treatment, probably mediated by an increased number of matrix synthesizing cells, as judged by augmentation of the DNA content in the presence of unaltered Hyp/DNA and RNA/DNA ratios. The relative amount of type III collagen was increased after 500 mg/kg per day D-pen for 10 and 42 days. High doses of D-pen increased the percentage of water in the aortic wall and reduced the ratio of Hyp to total tissue protein, suggesting an increased content of water-binding substances. This was confirmed by GAG accumulation. Hyaluronic acid (HA) and chondroitin 4,6-sulphate (CHS) were predominant after 32 and 42 days, whereas CHS, heparan sulphate (HS) and dermatan sulphate (DS) prevailed after 70 days of treatment. These observations suggest that processes of repair and regeneration are elicited secondary to the inhibitory effect of D-pen on aortic collagen and elastin crosslinking. Hypertrophy of the vessel wall may imply an increased rigidity, resulting in further increase of the susceptibility to haemodynamic injury.

Animals↗

Acid glycosaminoglycans in myxoedema.

Acid glycosaminoglycans were measured in the tissues of a virtually untreated 83-year-old woman with myxoedema. Intercellular oedema was demonstrated histologically in the tongue, myocardium, striated muscles, and in the skin. Tissue oedema was absent in two female control patients. All tissues from the patient with myxoedema, apart from the stomach, showed high concentrations of hyaluronic acid, but there was no consistent elevation of chondroitin-4,6-sulphate, heparan sulphate or dermatan sulphate. The accumulation of hyaluronic acid might contribute to the oedema formation in myxoedema.

Aged↗