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Biomedical subjects

C H Jensen

Publications and source records attributed to C H Jensen.

At least 19 recordsLinked to original sources

Knee injury and obesity in patients undergoing total knee replacement: a retrospective study in 115 patients.

The prevalence of obesity and previous knee injury was assessed in a retrospective study of 115 patients under-going total knee replacement due to osteoarthritis. Obesity was considered a contributing factor in the development of osteoarthritis in 37% of the patients, and 33% of the patients had had an injury to the knee in question. Unilateral osteoarthritis was significantly more frequent than bilateral osteoarthritis among patients with a history of previous knee injury. The association of previous injury to the knee and unilateral osteoarthritis was stronger in men than women. Aggressive treatment of patients with knee injuries seems warranted.

Adult

Indirect measurement of mitochondrial proton leak and its application.

In mitochondria, ATP synthesis is coupled to oxygen consumption by the proton electrochemical gradient established across the mitochondrial inner membrane in a process termed oxidative phosphorylation. It has long been known from stoichiometric studies that ATP synthesis is not perfectly coupled to oxygen consumption. The major inefficiency in the system is leakage of protons across the mitochondrial inner membrane driven by the proton electrochemical gradient. The kinetics of the proton leak can be determined indirectly, by measuring the oxygen consumption of mitochondria under non-phosphorylating conditions (plus oligomycin) as a function of the proton electrochemical gradient. This experimental system provides a convenient means to investigate inner membrane permeability to protons and the effect of factors that may effect that permeability. In this paper we review some results from our laboratory of indirect measurement of mitochondrial proton leak and how it has been applied to investigate the effect of aging, obesity and thyroid status on proton leak. The results show that (i) proton leak in isolated liver mitochondria is not significantly different in a comparison of young and old rats, in contrast (ii) there is an apparent increase in proton leak in in situ mitochondria in hepatocytes from old rats when compared to those from young rats, (iii) proton leak in neuronal mitochondria in situ in synaptosomes is not significantly different in young and old rats, (iv) proton leak is greater in isolated liver mitochondria from ob/ob mice compared to lean controls, (v) acute leptin (OB protein) administration restores the increased leak rate in isolated liver mitochondria from ob/ob mice to that of lean controls, (vi) administration of thyroid hormone (T3) increases proton leak in rat muscle mitochondria, and (vii) proton leak in muscle mitochondria is insensitive to the presence of GDP. It is proposed that the experimental system described here for measuring proton leak, is an ideal functional assay for determining whether the novel uncoupling proteins increase inner membrane permeability to protons.

Aging

Fetal antigen 1, a member of the epidermal growth factor superfamily, in neurofibromas and serum from patients with neurofibromatosis type 1.

Fetal antigen 1 (FA1) is a 26-32 kDa glycoprotein containing six epidermal growth factor-like repeats closely related to the delta/notch/serrate proteins in Drosophila. FA1 has been shown to be involved in cell differentiation in a juxtacrine/paracrine manner. As neurofibromatosis type 1 (NF-1), also called von Recklinghausen disease, involves aberrant growth of tissues derived from the neural crest, the expression of FA1 was examined in neurofibroma skin biopsies and serum from patients with NF-1. FA1 was found in the spindle cells of all (n = 10) skin tumour specimens from adult NF-1 patients, whereas normal dermis was FA1 negative. In adults, the serum FA1 levels were significantly higher in NF-1 patients (n = 13) than in normal healthy controls (n = 177) (P = 0.037). In the group of children with NF-1 (n = 9), significantly higher serum FA1 levels were observed in those known to have complications with cerebral or spinal involvement (n = 4) (P = 0.014). The presence of FA1 in neurofibroma specimens and the elevated serum levels in patients with NF-1 suggests that FA1 may be involved in the pathogenesis of NF-1, perhaps acting as a growth promoting factor.

Adolescent

Fetal antigen 1, an EGF multidomain protein in the sex hormone-producing cells of the gonads and the microenvironment of germ cells.

Fetal antigen 1 (FA1), an epidermal growth factor (EGF) multidomain glycoprotein, was investigated in the human reproductive system. Immunohistochemical analysis of the male reproductive system revealed staining for FA1 in the Leydig cells only. Concentrations of FA1 in seminal plasma and serum were similar and significantly correlated in weekly samples from three men (P < 0.0065). The concentrations in seminal plasma from vasectomized men (n = 4) were not significantly different from those of normal men (n = 187). The concentration of FA1 in seminal plasma was significantly correlated with the sperm counts of normozoospermic men (P < 0.0001), and significantly higher in seminal plasma from men with sperm counts > 20 x 10(6)/ml, compared with those with counts </= 20 x 10(6)/ml (P < 0. 0001). Immunohistochemical analysis of the ovary showed the presence of FA1 in the theca interna and the hilus cells but not in the granulosa cells or the oocyte. In follicular fluid the concentration of FA1 (median; 73.3 ng/ml, n = 28) was three times higher than that of serum (median; 23.8 ng/ml). These data suggest a role for this novel member of the EGF superfamily in relation to human reproduction, but further experiments are needed to define the biological function and to elucidate its clinical potential.

Adult

Thermal instability of the trimeric structure of the N-terminal propeptide of human procollagen type I in relation to assay technology.

The N-terminal propeptide of procollagen type I (PINP) appeared in two peaks after size chromatography. The high-molecular weight form was transformed to the low-molecular weight form during incubation at 37 degreesC, whereas the low-molecular weight form remained unchanged. The PINP concentrations in amniotic fluid and sera remained unchanged during 37 degreesC incubation when measured using an ELISA; however, concentrations decreased by 89-93% when measured using an RIA. The ELISA:RIA ratio varied from 1.1 to 2.9 in these fluids because of different size distributions and the inability of the RIA to measure the low-molecular weight form. Thermal transition of the high-molecular weight form caused a change in its elution volume but did not change its migration in sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Mass spectrometry revealed identical results for both forms. We reached the following conclusions: (a) the trimeric structure of PINP is unstable at 37 degreesC; (b) the two molecular forms represent intact alpha1 chains in trimeric and monomeric forms; (c) thermal transition is an ongoing in vivo process; and (d) this is important in the choice of assay technology.

Amniotic Fluid

[Shoulder instability].

The importance of the labrum and glenohumeral ligament complex for the stability of the shoulder joint has been known since the beginning of this century. Shoulder instability may be classified into two large groups. TUBS, characterized by Traumatic, Unidirectional instability and Bankart lesion which often requires Surgery. The second group AMBRI, is characterized by Atraumatic, Multidirectional, Bilateral instability that often responds to Rehabilitation, but in case of surgery Inferior capsular shift is indicated. The high recurrence rate after primary traumatic anterior dislocation in young adults has caused an ongoing discussion about the indications for primary surgery. Anatomical reconstruction focusing on the pathoanatomy is recommended due to better results and a lower complication rate as compared to non-anatomical reconstruction that alters the normal anatomy and kinematics. The recurrence rate after arthroscopic Bankart repair is still generally higher than after open surgery but may be improved by better patient selection.

Adult

Quantification of the N-terminal propeptide of human procollagen type I (PINP): comparison of ELISA and RIA with respect to different molecular forms.

This paper compares the results of procollagen type I N-terminal propeptide (PINP) quantification by radioimmunoassay (RIA) and enzyme linked immunosorbent assay (ELISA). PINP in serum from a patient with uremic hyperparathyroidism was measured in RIA and ELISA to 20 micrograms l-1 and 116 micrograms l-1 and the corresponding concentrations in dialysis fluid were 94.5 micrograms l-1 and 140 micrograms l-1, respectively. PINP antigen appears in two distinct peaks following size chromatography and the two peak fractions display immunological identity and identical M(r)'s (27 kDa: SDS-PAGE). Analysis of fractions from size separated amniotic fluid, serum and dialysis fluid demonstrated that the RIA failed to measure the low molecular weight form of PINP. However, the anti-PINP supplied with the RIA-kit and the anti-PINP applied in the ELISA reacted equally well with both molecular forms of PINP when analysed in a direct ELISA. It is concluded that the major difference in the ELISA and RIA results is due to assay efficacy with respect to the low molecular weight form of PINP.

Amniotic Fluid

Interlocking nailing of humeral shaft fractures.

: In this retrospective study 48 humeral shaft fractures in 48 patients were operated on using the Seidel interlocking nail. The length of follow-up ranged from 6 to 60 months (median, 26 months). The treatment of fractures was satisfactory with the Seidel nail, but we emphasize the importance of countersinking the tip of the nail into the humeral head to avoid impingement. In 5 of 12 patients with non-unions, the procedure failed, and we found that the distal locking seemed to be inadequate. Pathological fractures (i.e., those caused by metastatic tumors) were all efficiently treated with the Seidel nail.

Adult

Fetal antigen 1 (FA1), a circulating member of the epidermal growth factor (EGF) superfamily: ELISA development, physiology and metabolism in relation to renal function.

We describe an ELISA technique for quantification of fetal antigen 1 (FA1), a glycoprotein belonging to the EGF-superfamily. The ELISA is based on immunospecifically purified polyclonal antibodies and has a dynamic range of 0.7-5.3 ng/ml, intra- and inter-assay C.V.s of less than 3.2% and an average recovery of 105% in serum and 98% in urine. Comparison of FA1 in amniotic fluid, serum and urine revealed parallel titration curves, identical elution volumes following size chromatography, immunological identity and similar profiles when analysed by MALDI-MS. The reference interval for serum FA1 was 12.3-46.6 ng/ml and the levels were 10 times higher in patients with renal failure. FA1 showed no diurnal variation, no variation during the menstrual cycle and was not influenced by the acute phase reaction. In humans (n = 10) the renal clearance of FA1 was 11 ml/min and an identical high renal clearance was found in rats when expressed per 100 g body weight. In rats the initial increase in serum FA1 was 10 ng/ml/h following bilateral nephrectomy, explaining the increased serum concentrations of FA1 observed in patients with renal failure.

Acute-Phase Reaction

Magnetic resonance imaging-determined synovial membrane and joint effusion volumes in rheumatoid arthritis and osteoarthritis: comparison with the macroscopic and microscopic appearance of the synovium.

OBJECTIVE: To evaluate the relationship between synovial membrane and joint effusion volumes determined by magnetic resonance imaging (MRI) and macroscopic and microscopic synovial pathologic findings in patients with rheumatoid arthritis (RA) and osteoarthritis (OA). METHODS: Synovial biopsies were performed, and macroscopic grades of synovitis assigned, at preselected knee sites during arthroscopy or arthrotomy in 17 knees with RA and 25 with OA. Synovial inflammation and 9 separate tissue characteristics were graded histologically. Synovial membrane and joint effusion volumes were determined by preoperative MRI, enhanced with intravenous gadopentetate dimeglumine. RESULTS: MRI-determined synovial membrane volumes were correlated with the overall histologic assessment of synovial inflammation (Spearman's sigma = 0.55, P < 0.001), with fibrin deposition, with subsynovial mononuclear and polymorphonuclear leukocyte infiltration (sigma = 0.51-0.59), and less significantly with macroscopic synovitis, vessel proliferation, and granulation tissue formation (sigma = 0.40-0.42). No correlation with synovial lining multiplication, perivascular edema, villous formation, or fibrosis was found (sigma < 0.30). CONCLUSION: MRI-determined synovial volumes are correlated with synovial inflammatory activity. Synovial volumes probably mainly reflect the mass of cell-infiltrated, vascularized subsynovial tissue, but may also be influenced by the cumulative synovial proliferative activity. MRI-determined synovial membrane and effusion volumes may be sensitive markers and/or predictors of disease activity and treatment outcome in RA.

Adult

FA1 immunoreactivity in endocrine tumours and during development of the human fetal pancreas; negative correlation with glucagon expression.

Fetal antigen 1 (FA1) is a glycoprotein containing six epidermal growth factor (EGF)-like repeats. It is closely similar to the protein translated from the human delta-like (dlk) cDNA and probably constitutes a proteolytically processed form of dlk. dlk is homologous to the Drosophila homeotic proteins delta and notch and to the murine preadipocyte differentiation factor Pref-1. These proteins participate in determining cell fate choices during differentiation. We now report that FA1 immunoreactivity is present in a number of neuroectodermally derived tumours as well as in pancreatic endocrine tumours. A negative correlation between FA1 and glucagon immunoreactants in these tumours prompted a reexamination of FA1 immunoreactants during fetal pancreatic development. At the earliest stages of development, FA1 was expressed by most of the non-endocrine parenchymal cells and, with ensuing development, gradually disappeared from these cells and became restricted to insulin-producing beta cells. Throughout development FA1 was not detected in endocrine glucagon, somatostatin or pancreatic polypeptide cells. Moreover, developing insulin cells that coexpressed glucagon were negative for FA1. Thus, there was a negative correlation between FA1 and glucagon both in tumours and during development. These results, together with FA1/dlk's similarity with homeotic proteins, point to a role of FA1 in islet cell differentiation.

Antibodies, Monoclonal

Procollagen type I N-terminal propeptide (PINP) as an indicator of type I collagen metabolism: ELISA development, reference interval, and hypovitaminosis D induced hyperparathyroidism.

A sandwich enzyme-linked immunosorbent assay (ELISA) for quantification of the N-terminal propeptide of human procollagen type I (PINP) utilizing purified alpha 1-chain specific rabbit antibodies is described. The ELISA measured the content of the alpha 1-chain of PINP independent of the molecular form of the molecule. A parallelism was found between amniotic fluid (calibrator), normal and patient serum, and purified PINP (alpha 1), as well as the high and low molecular weight forms of PINP (alpha 1). The concentration of PINP in the calibrator (second trimester amniotic fluid) was determined to 25 micrograms/mL and the detection limit was 62 pg/mL measured in amniotic fluid, and 41 pg/mL measured in serum. The interassay coefficients of variation were 4.6% (low control) and 5.3% (high control), and the corresponding intraassay parameters were 2.9% and 4.9%. Recovery studies revealed an accuracy between 93% and 105%. The normal range (n = 57) for PINP was 56 ng/mL (median) the 10th and 90th centiles being 30 and 82 ng/mL, respectively. Patients with hyperparathyroidism due to hypovitaminosis D had median serum level of 168 ng/mL with a 10th centile of 44 ng/mL and a 90th centile of 450 ng/mL, these values being significantly different from the normal range (p < 0.001). The PINP-ELISA was superior to commercially available assays for PICP and osteocalcin in separation between healthy controls and patients with osteomalaci.

Adult

Biodegradable pins versus Kirschner wires in hand surgery.

We compared biodegradable pins with standard Kirschner wires in the fixation of fractures, arthrodeses and osteotomies in the hand in a prospective, randomized study. Eleven patients were allocated to the biodegradable pin group and 12 to the Kirschner wire group. Age, gender, operative procedure and postoperative treatment did not differ in the two groups. All patients were evaluated after 6 months. No differences in time to union or complication rates were found, but the number of additional operative procedures in the Kirschner wire group significantly exceeded the number needed in the biodegradable pin group.

Adult

Further investigations of the intraosseous pressure characteristics in necrotic lunates (Kienböck's disease).

To confirm the hypothesis that venous congestion plays a role in idiopathic lunate necrosis (Kienböck's disease), intraosseous pressure in 12 normal and 12 necrotic lunates was measured. Intraosseous pressure in the capitate of 12 healthy subjects served as reference measurement. The intraosseous pressure was recorded in neutral position and 60 degrees extension of the wrist under normotensive conditions and during venous stasis. In all groups, the mean intraosseous pressure rose significantly with extension of the wrist, with the largest increase being 92.3 mmHg for necrotic lunates, followed by 40.3 mmHg for normal lunates, 6.9 mmHg for normal capitates and during venous stasis, 26.6 mmHg for necrotic lunates, 26.1 mmHg for normal lunates, and 5.9 mmHg for normal capitates. In some necrotic lunates, the intraosseous pressure during extension exceeded the arterial blood pressure, which can be explained by mechanical deformation of the bone. In neutral position, no significant differences in pressure were found between normal lunates and capitates. A significant difference was found for venous stasis and extension. The intraosseous pressure rise in the normal lunate in extension was slightly higher than the pressure found during venous stasis. The intraosseous pressure differed significantly (by 56.9 mmHg) between normal and necrotic lunates in extension. These data support the hypothesis that impairment of venous drainage plays a role in lunate necrosis and that the lunate can be considered as a venous bone at risk.

Adult

Idiopathic avascular necrosis of the scaphoid in a child.

A 10-year-old boy presented with a one month history of pain in his right (dominant) wrist. He was treated by immobilisation for three weeks with little improvement. By 28 months later his symptoms had settled and activities were unrestricted. Radiographic examination showed unaltered fragmentation of the scaphoid and radial subluxation of the capitate. To our knowledge this is the first report of avascular necrosis of the scaphoid in a child.

Age of Onset

Protein structure of fetal antigen 1 (FA1). A novel circulating human epidermal-growth-factor-like protein expressed in neuroendocrine tumors and its relation to the gene products of dlk and pG2.

The present paper describes the primary structure, glycosylation and tissue localization of fetal antigen 1 (FA1) isolated from second-trimester human amniotic fluid. FA1 is a single-chained, heterogeneous glycoprotein of 225-262 amino acid residues. FA1 has six well conserved epidermal-growth-factor motifs and contains up to ten O-glycosylation and N-glycosylation sites, six of which are differentially glycosylated. Alignment to the translated sequences of Mus. musculus dlk and human dlk revealed 86% and 99% identity, respectively, to a 259-amino-acid residue overlap, and this high similarity extends with minor corrections to the human adrenal-specific mRNA, pG2 as well. Immunohistochemical analysis demonstrated the presence of FA1 in 10 out of 14 lung tumors containing neuroendocrine elements, and in the placental villi where FA1 was exclusively seen in stromal cells in close contact to the vascular structure. In the pancreas, FA1 co-localized with insulin in the insulin secretory granules of the beta cells within the islets of Langerhans. Our findings suggest that FA1 is synthesized as a membrane anchored protein and released into the circulation after enzymic cleavage, and that circulating FA1 represents the post-translationally modified gene product of human dlk which, in turn, is identical to human adrenal-specific mRNA pG2.

Amino Acid Sequence