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Biomedical subjects

P Junker

Publications and source records attributed to P Junker.

At least 73 records · Page 4Linked to original sources
PubMed1986

Serum markers for type IV collagen and type III procollagen in the myelofibrosis-osteomyelosclerosis syndrome and other chronic myeloproliferative disorders.

Myelofibrosis is characterized by excessive deposition of interstitial and basement membrane collagens in the bone marrow. In this study, specific radioimmunoassays for the aminoterminal propeptide of type III procollagen and for the 7S collagen domain of type IV (basement membrane) collagen were used to determine how this accumulation is reflected in serum. Of the 41 patients with chronic myeloproliferative disorders studied, the highest levels of both parameters were found in idiopathic myelofibrosis and in chronic myelogenous leukaemia associated with bone marrow fibrosis. Increasing degrees of bone marrow fibrosis were accompanied by increasing serum concentrations of both markers, except for osteomyelosclerosis, where notably low values were seen. Pathologically high values of one or both parameters were also found in a few patients with polycythaemia vera or a transitional myeloproliferative disorder. The antigens related to type III procollagen and type IV collagen correlated significantly with each other and with the leucocyte count. These parameters should provide noninvasive means for following the accumulation of interstitial and basement membrane collagens in the bone marrow.

Adult↗
PubMed1986

Serum amino-terminal type III procollagen peptide in rheumatoid arthritis. Relationship to disease activity, treatment, and development of joint erosions.

Using 2 radioimmunoassays, increased serum levels of amino-terminal type III procollagen peptide and its degradation products were demonstrated in rheumatoid arthritis patients. Patients with active disease showed higher serum propeptide levels than did patients with inactive disease. Unlike D-penicillamine, azathioprine treatment suppressed the propeptide levels in patients with active disease. A 6-month prospective study showed significantly higher initial serum propeptide levels in patients with erosive progression. The propeptide level reflects disease activity and may be a valuable prognostic marker in rheumatoid arthritis.

Adult↗
PubMed1985

Serum procollagen III peptide in chronic myeloproliferative disorders.

Using a radioimmunoassay the serum concentration of the N-terminal propeptide of type III procollagen (P-III-P) was measured in 35 patients with chronic myeloproliferative disorders, including idiopathic myelofibrosis (n = 10), osteomyelosclerosis (n = 4), transitional myeloproliferative disorder (n = 5), polycythaemia vera (n = 10) and chronic myelogenous leukaemia (n = 6). The normal range in 35 healthy controls was 4.9-11.7 ng/ml. The serum concentration of P-III-P increased with increasing degrees of bone marrow reticulin fibrosis. By contrast, almost normal levels were detected in osteomyelosclerosis with an indolent clinical course, in which an excessive deposition of mature collagen fibres was found, representing mainly type I collagen. These observations indicate that the serum P-III-P level is positively correlated to the degree of bone marrow reticulin fibrosis, whereas levels are near normal in patients with osteomyelosclerosis and stable disease. Measurement of serum P-III-P may be a useful indicator of disease activity in myelofibrosing conditions.

Adult↗
PubMed1984

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↗
PubMed1984

Effect of D-penicillamine pre- and post-implantation treatment on formation of sponge-induced granulation tissue in rats.

DNA, collagen and sulfated glycosaminoglycans (GAGs) of rat sponge granulation tissue were studied after 42 days of D-penicillamine (D-pen) treatment at 100, 250 or 500 mg/kg/day, starting 10 days before or 28 days after induction of granulation tissue formation. The effects were compared with those observed when the same dosage was started at the onset of the granulation tissue formation and with pair-fed controls. D-pen stimulated the cell invasion into the sponge implants, as manifested by an increased DNA content, particularly with pre-treatment. Pre-treatment reduced the net deposition of of collagen per cell as assessed by the lower hydroxyproline/DNA ratio, at the lower dose leading to reduced collagen concentration. The total amount of granulation tissue collagen remained essentially unaffected within the observation period. Salt-soluble collagen was augmented in a dose-dependent manner, irrespective of treatment protocol, signifying decreased collagen cross-linking. Both pre- and post-implantation treatment enhanced the radiosulfate incorporation into sulfated GAGs, regardless of dose, whereas treatment from the day of sponge implantation had no effect. It is concluded that D-pen enhances the early connective tissue response to injury. Reduction of collagen cross-linking and net collagen deposition, concomitant with stimulation of the proteoglycan metabolism, may pertain to the antirheumatoid activity of D-pen. The observations suggest that long-term administration of D-pen, starting before new attacks of arthritis, may be most effective in controlling developing articular fibrosis.

Animals↗
PubMed1983

Reversibility of D-penicillamine induced collagen alterations in rat skin and granulation tissue.

Granulation tissue was produced in rats by subcutaneous implantation of Visella sponges. D-penicillamine (D-pen) 100 or 500 mg/kg was administered daily for 42 days by gastric tubing. Pairfed, placebo treated animals were included as controls. Half of the groups were kept for additionally 28 days without medication. The inhibitory effect of D-pen on cross-link formation in newly synthesized collagen was readily reversible. By contrast, cross-link deficiency lasting beyond the observation period was observed in the higher polymeric collagen variants released by dilute acid, heat exposure or limited pepsin proteolysis as estimated by solubility, alpha/beta chain ratio and/or aldehyde content. By SDS-polyacrylamide gel electrophoresis on gels containing 3.6 M urea it was shown that purified dermal acid soluble collagen from treated animals consisted of a mixture of type I and III collagen, whereas only type I collagen was detected in controls. The band pattern was identical in reduced and unreduced collagen samples. Four weeks after D-pen discontinuance type III collagen had disappeared from the acid extract. Moreover, the ratio of type III to type I collagen in the pepsin digest from both granulation tissue and skin showed a persistent rise with D-pen. These observations indicate that D-pen destabilized type III collagen in particular by interference with its disulfide linkages. The amount of granulation tissue remained unaffected throughout the experiment, whereas the skin collagen content decreased at the higher dose level. The regeneration was not completed by the end of the observation period. Modulation of the molecular stability of granuloma collagens may be of relevance for the antirheumatoid effect of D-pen, but the sustained effect on normal tissues may imply a long standing impairment of their supportive capacity.

Animals↗
PubMed1983

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↗
PubMed1982

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↗
PubMed1982

The effect of D-penicillamine and methylprednisolone on the morphology of experimental granulation tissue in rats.

The effects of D-penicillamine and methylprednisolone on the formation of granulation tissue was studied in rats with Visella-sponge induced granulation tissue after 42 days of treatment. D-penicillamine in doses of 20 mg-, 100 mg-, 500 mg/kg/day caused no morphological differences compared with the control groups as regards ingrowth of granulation tissue and its content of collagen fibres, inflammatory cells, vessels and glycosaminoglycans. Treatment with methylprednisolone, 0.2 mg-, 2.0 mg-, and 5.0 mg/kg/day caused a dose dependent reduction in the ingrowth of granulation tissue. Methylprednisolone caused a reduction in the number of fibroblasts and collagen fibres, but no differences in the content of glycosaminoglycans could be demonstrated between the treated and the control groups. Granulation tissue produced during combination treatment with D-penicillamine 100 mg and methylprednisolone 2.0 mg/kg/day did not differ from that observed after methylprednisolone treatment alone. Thus, only high doses of methylprednisolone gave rise to an antiinflammatory action in this morphological study on granulation tissue, whereas D-penicillamine had no effect within the present dose interval. The quantitative alterations are in agreement with parallel biochemical analyses. However, the inhibitory effect of D-penicillamine on collagen crosslinking was not associated with light microscopic changes in the ultrastructure of the collagen fibres.

Animals↗
PubMed1982

Fibronectin in experimental granulation tissue.

The temporal appearance of fibronectin in experimental granulation tissue has been studied using the immunoperoxidase technique on material fixed in formaldehyde, embedded in paraffin and pretreated with pepsin. Furthermore, the relationship between the distribution of fibronectin and connective tissue fibres, demonstrated as either argyrophilic or red by the van Gieson method, has been investigated. Fibronectin was demonstrated as part of the fibrinous network in the sponge before the formation of granulation tissue. In the development of granulation tissue fibronectin was seen in the initial cellular stage codistributed with the newly formed fibres, first the argyrophilic fibres and later with those stained red by the van Gieson method, too. With maturation of the granulation tissue, predominated by these fibres, the amount of fibronectin was gradually reduced. The presence of fibronectin in the sponge already before the formation of granulation tissue suggests that fibronectin in the initial stage of inflammation derives from plasma. The increase in amount of fibronectin corresponding to the cellular (fibroblastic) proliferation and the formation of fibres, both argyrophilic and van Gieson positive, indicates that fibronectin in young granulation tissue is synthesized by fibroblastic cells. The relationship between the morphologically demonstrated argyrophilic fibres and van Gieson positive fibres and the biochemical type III and type I collagens is discussed.

Animals↗
PubMed1981

Effect of different doses of D-penicillamine and combined administration of D-penicillamine and methylprednisolone on collagen, glycosaminoglycans, DNA and RNA of granulation tissue, skin, bone and aorta in rats.

D-penicillamine (D-pen) in doses of 20, 100 and 500 mg/kg/day or D-pen 100 mg/kg/day plus methylprednisolone (MP) 2.0 mg/kg/day was administered daily for 42 days to rats implanted with viscose-cellulose sponges. Operated, pairfed rats served as controls. D-pen increased the DNA content of granulation tissue, but had no effect on the amount of tissue produced. In contrast, high dose D-pen reduced the content of DNA and collagen in skin. A dose related inhibition of collagen crosslink formation occurred in all tissues, particularly in skin, as indicated by increased proportions of extractable collagen with increased alpha/beta chain ratio and aldehyde content. Moreover, low doses of D-pen increased the hydroxyproline/proline ratio of acid soluble skin collagen, presumably due to solubilization of type III collagen as demonstrated by SDS-polyacrylamide gel electrophoresis in the presence of 3.6 M urea. These changes were associated with increased skin fragility and edema plus excess elastin deposition in the aorta after high dose D-pen treatment. Low dose D-pen stimulated the 35S-sulphate uptake into the sulphated glycosaminoglycans (GAGs) of granulation tissue without altering their relative amounts, whereas high dose D-pen reduced the concentration of chondroitin-4/6-sulphate in skin. MP antagonized the solubilizing effect of D-pen on collagen, probably by inhibition of the collagen synthesis. In addition, MP inhibited the cell proliferation and GAG metabolism. Food restriction reduced the DNA content of granulation tissue. The inhibitory effect of D-pen on the formation of granuloma collagen crosslinks in the presence of unaltered rate of collagen biosynthesis may diminish the amount of fibrotic tissue due to increased degradability of crosslink deficient collagen. Simultaneous administration of MP may facilitate this effect by inhibiting the biosynthesis of collagen. However, long-term D-pen treatment seems to increase the susceptibility of normal tissues to mechanical injury.

Animals↗
PubMed1981

Effect of D-penicillamine on collagen, glycosaminoglycans, DNA and RNA of granulation tissue and connective tissue of skin, bone and aorta in rats.

Granulation tissue was produced by subcutaneous implantation of viscose-cellulose sponges on rats. The effect of D-penicillamine 500 mg/kg/day for 10 days on granulation tissue and the connective tissue of skin, bone and aorta was studied ny comparison of treated animals with operated and unoperated controls. In addition, the effect of sponge implantation on intact tissues was studied by comparison between the control groups. The amount of granulation tissue was not affected by D-penicillamine, and the granulomas-DNA content even increased. D-penicillamine increased the amount of salt soluble collagen in all tissues consistent with an inhibition of collagen crosslinking as reflected by increased aldehyde content and alpha/beta chain ratio in soluble skin collagen. Skin appeared to be most sensitive. The content of free hydroxyproline and RNA and the RNA/DNA ratio in skin decreased suggesting a decreased collagen biosynthesis. The hydroxylation of proline and lysine was not affected by the treatment. The water percentage of aorta increased during D-penicillamine treatment, and the 35S-sulphate uptake in the sulphated glycosaminoglycans was stimulated in all tissues, in granulation tissue mainly in the chondroitin-4/6-sulphate fraction. No quantitative glycosaminoglycan changes occurred in granulation tissue. Sponge implantation caused an increase in the amount of salt soluble skin collagen without any change in alpha/beta chain ratio and aldehyde content of purified, soluble collagen. D-penicillamine plus operation reduced the collagen content of aorta. The effects of D-penicillamine on connective tissue compounds may be of importance for its antirheumatic efficacy, but the accompanying effect on normal tissues may imply side effects.

Animals↗
PubMed1979

Prednisone effect on microvascular permeability in patients with inflammatory rheumatic diseases.

The transcapillary escape rate of albumin was measured in 27 consecutive patients with inflammatory rheumatic diseases before and after 1 and 7 days of prednisone treatment in doses of 45 mg/day. The transcapillary escape rate decreased from 7.33%/h (range 5.11-9.55) before prednisone treatment to 3.11%/h (0.04-6.18) (p less than 0.05) after 1 day of treatment and 5.80%/h (4.36-7.24) after 7 days of treatment. It is concluded that prednisone inhibits vascular permeability in patients with inflammatory rheumatic diseases.

Adult↗
PubMed1979

Formation of granulation tissue in subcutaneously implanted sponges in rats. A comparison between granulation tissue developed in viscose cellulose sponges (Visella) and in polyvinyl alcohol sponges (Ivalon).

A comparison was made between the granulation tissue formation in two different synthetic sponge types. Visella and Ivalon, of different sizes. The granulation tissue formed in the two sponge types did not differ qualitatively, and had the character of wound tissue and inflammatory tissue in man. The rate of tissue formation in the Visella sponges was faster and the tissue was more homogenous than in the Ivalon sponges. Fourteen-day-old Visella implants of either size contained more granulation tissue than Ivalon sponges, probably owing to the smaller pore size of the former material. This may also account for the more frequent occurrence of giant cells in the Visella implants. In contrast to the Visella sponges, the trabeculae of the Ivalon polymer showed calcification and positive staining properties with histological staining procedures, and deformation was frequent among the Ivalon implants. Thin sponges of either type closed in about 21 days, thick ones after about 42 days of implantation. Calculated per 2 cm3 of implant, thin sponges produced more tissue after 14 days of implantation than thick noes. It is concluded that the Visella sponge type is best suitable for this experimental model of inflammation.

Animals↗
PubMed1976

Umbilical vein catheterization and portal hypertension.

Portal hypertension is a rarely encountered late complication of umbilical vein catheterization. A survey of the 38 cases previously published is presented together with an additional case report. It is concluded that catheterization for more than 2 days carries an increased risk of thrombosis, and that umbilical artery catheterization should be preferred in the majority of cases due to a reduced risk of complications. The correct position of the catheter tip must always be controlled by fluoroscopy or X-ray. Infusion of hypertonic solutions with unphysiological pH should be restricted and umbilical vessel catheterization should only be carried out in severe cases. Pretreatment of the catheters with heparin possibly reduces the hazards.

Catheterization↗