PubMed Health⌕ Search

Biomedical subjects

L Heickendorff

Publications and source records attributed to L Heickendorff.

At least 73 records · Page 4Linked to original sources
PubMed1996

Effect of insulin and growth hormone on the synthesis of radiolabelled proteoglycans from cultured human arterial smooth-muscle cells.

The present study focuses on the pathogenesis of increased frequency of large-vessel disease in diabetes. The diabetic arterial wall displays characteristic alterations of the extracellular matrix secreted by arterial smooth-muscle cells. The effects of insulin and growth hormone on the synthesis of sulphate-labelled proteoglycans and heparan sulphate proteoglycan were studied. Proteoglycans and heparan sulphate proteoglycan were obtained from the medium and the cell layer of cultured human arterial smooth-muscle cells grown in 5% human serum. Heparan sulphate proteoglycan was quantified using ethanol precipitation combined with specific enzyme degradation. Addition of insulin (0.01, 0.05 and 0.10 mU/ml) induced a significant accumulation of 35S-labelled proteoglycans in the cell layer (2p < 0.005 and 2p < 0.001). The relative amount of cell-associated heparan sulphate proteoglycan increased during insulin stimulation (2p < 0.05). Growth hormone stimulation (5.0 and 10.0 ng/ml) caused a significant decrease in the ratio between heparan sulphate proteoglycan and proteoglycan in the cell layer (2p < 0.02 and 2p < 0.01), whereas the distribution of proteoglycans between the cell layer and the medium was unaltered.

Aorta↗
PubMed1996

Treatment of ischaemic digital ulcers and prevention of gangrene with intravenous iloprost in systemic sclerosis.

Twelve patients with systemic sclerosis were treated with intravenous infusions of the prostacyclin-stable analogue iloprost 0.5-2.0 ng/kg/min for 6 h from 8 to 13 days. Imminent gangrene was stopped in 2 patients and followed by healing. In 4 of 6 patients iloprost led to complete healing of ischaemic ulcers and in the remaining 2 patients to partial healing. One patient with severe Raynaud's phenomenon discontinued the study after 3 days due to severe headache. The 2 remaining patients with Raynaud's phenomenon as an indication improved, while no improvement was recorded in a patient with vasculitis of the lower leg. Side-effects such as headache, nausea and flushing were the reason that only 5 patients reached the maximum infusion rate. No statistical differences were recorded in digital bloodflow before and after the study or in plasma endothelin in the 9 patients investigated. Three of the 6 patients with healing ulcers, however, showed a pronounced decrease in plasma endothelin. Iloprost appears useful as a treatment of imminent gangrene and ischaemic ulcers in systemic sclerosis. This reparatory capacity could also be of a more general importance in therapy of this disease.

Adult↗
PubMed1996

Plasma endothelin in psoriasis: possible relations to therapy and toxicity.

Plasma endothelin levels were studied in 71 patients suffering from severe psoriasis. The psoriatics were treated either with topical therapy alone (n = 18) or with cyclosporin A (n = 26), methotrexate (n = 21), or with hydroxyurea, acitretin or ranitidin (n = 6) with or without topical therapy. The psoriatics had a significantly higher average plasma endothelin than 40 healthy controls. The patients treated with cyclosporin A had the highest values and these were in contrast to patients on methotrexate and other systemic therapy higher than patients treated with topical therapy alone. There was not significant difference between endothelin levels in patients treated with methotrexate compared to those in patients only receiving topical treatment. Whether the increased endothelin levels in plasma are derived from keratinocytes or enlarged vessels need to be investigated. An increased plasma endothelin level could be related to therapy and for patients on cyclosporin A be of importance for toxicity.

Acitretin↗
PubMed1995

The use of serologic markers for collagen synthesis and degradation in systemic sclerosis.

BACKGROUND: Systemic sclerosis is characterized by excessive accumulation of collagen in all involved organs. Serum markers of collagen synthesis and degradation, the aminoterminal propeptide of type III procollagen (PIIINP), the carboxyterminal propeptide of type I procollagen (PICP), and the crosslinked telopeptide of type I collagen (ICTP), can be measured. OBJECTIVE: Our purpose was to investigate these markers in different subgroups of untreated patients with systemic sclerosis and in patients before and after various types of therapy. PIIINP and PICP were also investigated in blister fluid from involved and uninvolved skin. METHODS: Sera from 97 patients and suction blister fluid from 13 patients were radioimmunoassayed. RESULTS: The highest levels of PIIINP and PICP were found in blister fluid from involved skin. Patients with systemic sclerosis had higher serum levels of PIIINP than control subjects. The highest levels were found in patients with diffuse cutaneous systemic (type III) sclerosis; increased serum PIIINP was also characteristic of type II limited cutaneous systemic sclerosis. Most patients with limited cutaneous type I systemic sclerosis had normal levels. Serum PICP was within normal limits in all three types of systemic sclerosis. Variations in ICTP type I collagen degradation in general followed PICP. Immunosuppressive drugs significantly reduced PIIINP, whereas no significant decrease was found after photopheresis. PICP and ICTP also diminished after treatment with D-penicillamine and cyclophosphamide given together with prednisone. CONCLUSION: PIIINP can be recommended for monitoring collagen synthesis in systemic sclerosis. Our data support the use of immunosuppressive therapy for this disease.

Biomarkers↗
PubMed1994

Connective tissue components in serum in multiple myeloma: analyses of propeptides of type I and type III procollagens, type I collagen telopeptide, and hyaluronan.

The present study was performed to evaluate whether information concerning synthesis and degradation of type I collagen in multiple myeloma (MM) as obtained by serum analyses of C-terminal propeptide of type I procollagen (PICP) and the C-terminal telopeptide of type I collagen (ICTP) may be useful in evaluating the development of osteolytic bone destruction. Serum N-terminal propeptide of type III procollagen (PIIINP) may give information about marrow fibrosis in MM. No data are available about MM and serum hyaluronan, another important component of bone marrow stroma. We examined 15 consecutive patients before treatment and 15 sex- and age-matched controls. We found highly significant elevations in serum ICTP (median 6.2 vs. 2.4 micrograms/L; P < 0.01), PIIINP (median 5.2 vs. 2.9 micrograms/L; P < 0.01) and hyaluronan (median 122 vs. 45 micrograms/L; P < 0.01). ICTP in serum correlated closely to bone morbidity (r = 0.69; P < 0.01). Furthermore, serum ICTP correlated highly significantly to serum PIIINP (P < 0.01) and serum beta 2-microglobulin (P < 0.01), whereas there was no correlation between hyaluronan and any of the collagen-derived peptides or beta 2-microglobulin. The MM group was followed for 9-25 months and analysis of survival data suggested that serum ICTP may be of predictive value (P < 0.05). We conclude that important changes in connective tissue metabolism occur in MM. ICTP in serum seems to be a noninvasive marker of bone morbidity and may be of prognostic value. Furthermore, elevation of hyaluronan in serum is common in MM, the significance of which is unknown.

Aged↗
PubMed1994

Glycosaminoglycans in the human aorta in diabetes mellitus: a study of tunica media from areas with and without atherosclerotic plaque.

Alterations in the connective tissue of the arterial wall have been suggested to play a role in the development of macrovascular disease in diabetes mellitus. The present study deals with changes in the content of GAG in aortic tunica media in human diabetes by separately analysing normal areas and areas with fibrous plaques. The thoracic aorta from 15 diabetic patients (7 with IDDM, 8 with NIDDM), and 30 sex- and age-matched non-diabetic subjects were collected at autopsy. Tunica intima was removed and GAG were isolated from the dried defatted and pulverized tunica media. GAG were quantified by uronic acid analysis and characterized by electrophoresis on cellulose acetate. Results showed that IDDM patients had a relative and absolute increase in hyaluronic acid in normal tunica media compared to non-diabetic subjects. There was a significant positive correlation between hyaluronic acid content of normal tunica media and duration of diabetes, but not between hyaluronic acid content and age. When tunica media from plaque areas was compared to normal areas the same pattern was evident in diabetic patients as in non-diabetic patients--significantly increased proportion of dermatan sulphate and reduced hyaluronic acid. The data agree with the notion that the arterial wall is subject to different pathological processes in diabetes, one of classical atherosclerosis with changes in GAG similar to non-diabetic subjects, and the other seen in areas without plaques with dissimilar alterations in GAG. These data therefore support the concept of the presence of a macrovascular disease in diabetes different from atherosclerosis.

Aged↗
PubMed1994

A quantitative method for analysis of radiolabelled proteoglycans synthesized by cultured human arterial smooth muscle cells.

1. Sulphate labelled proteoglycans (PG) synthesized by cultured human arterial smooth muscle cell have been quantified using an improved method based on a combination of specific enzymes and ethanol precipitation. 2. The present method gives quantitative data of PGs and subclasses allowing batchwise analysis of a large number of samples. 3. Approximately 81% +/- 1.7% (mean +/- SD, n = 6) of total PGs synthesized by human arterial smooth muscle cells accumulated in medium. 4. In cell layer and medium chondroitin sulphate proteoglycan constituted 65.0% +/- 0.3% and 75.8% +/- 0.7% (mean +/- SD, n = 3), respectively of sulphated PGs. 5. Heparan sulphate proteoglycan accounted for 26.8% +/- 0.6% in cell layer and 22.6% +/- 0.5% (mean +/- SD, n = 3) in medium of sulphated PGs.

Aorta↗
PubMed1994

Serum propeptides of type I and III procollagens in renal transplant recipients. A comparison of cyclosporine and azathioprine treatment.

Chronic cyclosporine nephrotoxicity is characterized morphologically by cortical interstitial fibrosis. The most important collagens involved in renal fibrosis are collagen types I and III. In order to estimate the synthesis of type III and type I collagens, we analyzed serum levels of the amino-terminal propeptide of type III procollagen (PIIINP) and the carboxy-terminal propeptide of type I procollagen (PICP) in 11 renal transplant recipients receiving cyclosporine (group CY) and a comparable group of 16 renal transplant recipients treated with azathioprine (group AZ). In addition, 27 healthy subjects and 15 patients with chronic renal disease and reduced renal function (group CRD) were examined. The cyclosporine-treated patients had serum PIIINP and PICP similar to the azathioprine-treated patients. Both groups of renal transplant recipients had significantly increased serum PIIINP compared to healthy controls (2p < 0.01) and serum PIIINP levels similar to group CRD in which serum PIIINP was also elevated compared to healthy controls (2p < 0.01). Mean serum PIIINP levels were: group CY 0.81 U/l (n = 11); group AZ 0.98 U/l (n = 16); controls 0.62 U/l (n = 27); and group CRD 1.06 U/l (n = 15). The renal graft recipients--both cyclosporine- and azathioprine-treated patients--had significantly increased PICP serum levels compared to healthy controls, but the patients with chronic renal disease had serum PICP levels which did not differ from that of healthy controls. Mean serum PICP levels were: group CY174 micrograms/l; group AZ151 micrograms/l; controls 106 micrograms/l; and group CRD119 micrograms/l.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1994

Plasma endothelin and the aminoterminal propeptide of type III procollagen (PIIINP) in systemic sclerosis.

Forty-four patients with systemic sclerosis and 3 patients with localized scleroderma were investigated for plasma endothelin and aminoterminal propeptide of type III procollagen (PIIINP). Although there was an overlap between plasma levels of endothelin in patients with systemic sclerosis and healthy controls, the mean value of the patients was significantly higher than in controls. Plasma endothelin was normal in all 3 patients with localized scleroderma. The highest levels of plasma endothelin were found in patients with type II and III systemic sclerosis with the largest cutaneous involvement, and in patients with the scleroderma-specific antibodies Scl-70 and anticentromere antibodies. Extremely high values were found in a patient who experienced a renal crisis and in a patient who had her lower leg amputated due to severe vasculitis. A positive correlation was found between plasma endothelin and serum PIIINP. This, together with the fact that in systemic sclerosis the vascular lesions are the earliest, would seem to support the theory that endothelial cell damage could lead to increased secretion of endothelin and subsequent fibrosis in this disease.

Aged↗
PubMed1994

Skin scoring in systemic sclerosis: a modification--relations to subtypes and the aminoterminal propeptide of type III procollagen (PIIINP).

Forty-one patients with systemic sclerosis were investigated with a new and simple skin score method measuring the degree of thickening and pliability in seven regions together with area involvement in each region. The highest values were, as expected, found in diffuse cutaneous systemic sclerosis (type III SS) and the lowest in limited cutaneous systemic sclerosis (type I SS) with no lesions extending above wrists and ancles. A positive correlation was found to the aminoterminal propeptide of type III procollagen, a serological marker for synthesis of type III collagen. The skin score is considered simpler than previous methods and is recommended for more general use.

Arm↗
PubMed1993

Photopheresis in systemic sclerosis: clinical and serological studies using markers of collagen metabolism.

Eight patients with progressive systemic sclerosis were treated with photopheresis or extracorporeal photochemotherapy given on 2 consecutive days every 4 weeks for 5 to 8 months. Previous treatment with immunosuppressive agents or D-penicillamine was discontinued for at least 4 weeks prior to photopheresis. Although IL-2 receptor density in peripheral blood T-lymphocytes decreased significantly in the initial phase of the photopheresis therapy, no substantial clinical improvement occurred. Although the intention had been to treat all patients for at least 8 months with photopheresis alone, it was mandatory due to severe exacerbations to give additional immunotherapy to 4 patients, and 2 of these together with another patient wanted to discontinue photopheresis after 5 and 6 months, as they did not expect an effect. Three of the 4 patients with progression had RNP-antibodies, suggesting that they had their scleroderma as part of a mixed connective tissue disease. The clinical exacerbations were accompanied in all patients by a highly significant increase in serum aminoterminal propeptide of type III procollagen (PIIINP), which has been reported to correlate with involvement of skin and internal organs in systemic sclerosis. Similar but less significant increases were found in serum carboxyterminal propeptide of type I procollagen (PICP); there were no significant changes in serum cross-linked fragment of type I collagen. Plasma levels of 8-methoxypsoralen were all above 80 ng/l, showing that the lack of responses to photopheresis could not be due to poor absorption of the drug.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1991

Serum aminoterminal propeptide of type III procollagen in psoriasis and psoriatic arthritis: relation to liver fibrosis and arthritis.

Levels of serum aminoterminal propeptide of type III procollagen were measured in 170 patients with psoriasis (49% with coexistent psoriatic arthritis) who had liver biopsies performed during or before treatment with methotrexate or, in some cases, with retinoids. Psoriasis patients with fibrosis or cirrhosis in their liver biopsy specimens had a significantly higher mean serum aminoterminal propeptide of type III procollagen than did patients without fibrosis and without arthritis. Only 4% of patients without cirrhosis or fibrosis and no arthritis had an elevated serum aminoterminal propeptide of type III procollagen. In contrast, 38% of patients with psoriatic arthritis had an increased aminoterminal propeptide of type III procollagen in the absence of detectable liver fibrosis. It is concluded that the number of liver biopsies performed on methotrexate-treated psoriasis patients with or without arthritis may be reduced to a minimum as long as serum aminoterminal propeptide of type III procollagen is normal. Increased serum aminoterminal propeptide of type III procollagen in the absence of arthritis is a strong indicator of liver fibrogenesis and suggests the need for liver biopsy to monitor possible methotrexate-induced toxicity. In patients with psoriatic arthritis an increased aminoterminal propeptide of type III procollagen may be related to the joint disease. Patients with psoriatic arthritis and increased levels of aminoterminal propeptide of type III procollagen should therefore follow the established guidelines for the use of methotrexate in psoriasis.

Alkaline Phosphatase↗
PubMed1991

Skin symptoms among workers in the fish processing industry are caused by high molecular weight compounds.

Scratch tests were performed with fish juice containing high and low molecular weight compounds obtained by ultrafiltration and with degradation compounds known to accumulate in fish stored on ice. 75 volunteers were tested. The peptide pattern in raw fish juice and its high and low molecular weight fractions were analysed by sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE) and the concentration of protein in the various fractions was determined. Fish products were analysed for bacteria and algae and the concentration of degradation compounds was measured. Mainly high molecular weight compounds (polypeptides) of fish juice were found to be responsible for the skin symptoms.

Adolescent↗
PubMed1991

Serum aminoterminal propeptide of type III procollagen in systemic sclerosis. A follow-up--investigations in subclasses and during therapy.

Fifty-seven patients with systemic sclerosis were investigated for connective tissue turn-over related to type III collagen. Sera from 13 patients with diffuse cutaneous systemic sclerosis and 44 patients with limited cutaneous systemic sclerosis were analysed for aminoterminal propeptide of type III procollagen (PIIINP) by a radioimmunoassay based on human propeptide. Increased levels of PIIINP in serum correlated with skin involvement and the clinical course. All patients with diffuse cutaneous systemic sclerosis had levels above the normal range, and in limited cutaneous systemic sclerosis elevated PIIINP levels seemed to be correlated with rapid progression and with extension of lesions. Immunosuppressive drugs, cyclosporin A, and prednisone with or without cyclophosphamide, which were given to patients with rapid disease progression, significantly reduced PIIINP. This was also the case with penicillamine, but to a lesser degree. Our data support the suggestion that immunosuppressive agents are justified in rapidly progressive, life-threatening or disabling disease, when used with the necessary precautions. Serum PIIINP may be utilized as a marker of type III collagen fibrogenesis in systemic sclerosis and be of prognostic value. PIIINP may also be of use in the differential diagnosis between diffuse cutaneous systemic sclerosis and scleredema.

Drug Therapy, Combination↗
PubMed1990

Cyclosporin A treatment of systemic sclerosis.

Ten patients with severe progressive systemic sclerosis were treated with cyclosporin A at dosages of 1.5-7.5 mg/kg per day:two patients showed a marked improvement with softening of the involved skin; in one patient there was healing of persistent digital ulcers; one patient showed initial improvement followed by a marked exacerbation; one patient was slightly improved; two patients were unchanged. The clinical results correlated well with levels of serum aminoterminal propeptide of type III procollagen. In the eight patients completing treatment, side-effects such as slight tremor and a transient increase in the serum creatinine and blood pressure were either absent or reverted to normal when the dosage was decreased, except one case who had to be treated with anti-hypertensive drugs.

Adult↗
PubMed1989

Bioactive human recombinant tumor necrosis factor-alpha: an unstable dimer?

As determined by native polyacrylamide gel electrophoresis (PAGE) and gel chromatography the molecular mass of native tumor necrosis factor (TNF)-alpha was approximately 35 kDa. When incubated at low concentrations (less than 1 nM) 125I-labeled TNF-alpha and unlabeled TNF-alpha rapidly multimerized or dissociated into monomers and bioactivity decreased. Sodium dodecyl sulfate (SDS)-PAGE analysis of cross-linked 125I-labeled TNF-alpha demonstrated bands of multi- and trimeric TNF-alpha in addition to dominating bands of dimers and monomers. Tri-, di- and monomeric TNF-alpha were recovered from SDS-PAGE gels and allowed to renature. Of the original receptor-binding activity, 10%-15% was obtained with cross-linked TNF-alpha dimers, whereas none was recovered from preparations of trimeric TNF-alpha. Multimeric and monomeric TNF-alpha exhibited little or no binding activity, and cell-bound, cross-linked TNF-alpha which was dissociated from cellular binding sites was mainly dimeric. 125I-labeled TNF-alpha bound to lymphokine-activated killer (LAK) cells and binding kinetics were much similar (Kd approximately 100 pM) to those reported in other normal cell types. The number of receptors per LAK cell was approximately 4 x 10(3). Cross-linking of TNF-alpha to binding sites in U-937 and LAK cells yielded a receptor-ligand complex of about 80/90 kDa. At 37 degrees C, 125I-labeled TNF-alpha was rapidly internalized and degraded in L-929, U-937 and LAK cells. Degradation of ligand and recycling of receptors were blocked in the presence of methylamine. Methylamine significantly inhibited TNF-alpha-mediated cytolysis of L-929 cells and caused a quantitatively corresponding reduction in cellular TNF-alpha uptake, indicating that L-929 lysis was mediated by receptors.

Cell Survival↗