Biomedical subjects

J Pedersen

Publications and source records attributed to J Pedersen.

At least 37 records · Page 2Linked to original sources

PubMed2001

Human recombinant pro-dipeptidyl peptidase I (cathepsin C) can be activated by cathepsins L and S but not by autocatalytic processing.

Human dipeptidyl peptidase I was expressed in the insect cell/baculovirus system and purified in its active (rhDPPI) and precursor (pro-rhDPPI) forms. RhDPPI was very similar to the purified enzyme (hDPPI) with respect to glycosylation, enzymatic processing, oligomeric structure, CD spectra, and catalytic activity. The precursor, which was a dimer, could be activated approximately 2000-fold with papain. Cathepsin L efficiently activated pro-rhDPPI in vitro at pH 4.5 (k(app) approximately 2 x 10(3) min(-)(1) M(-)(1)), and two cleavage pathways were characterized. The initial cleavage was within the pro region between the residual pro part and the activation peptide. Subsequently, the activation peptide was cleaved from the catalytic region, and the latter was cleaved into the heavy and light chains. Alternatively, the pro region was first separated from the catalytic region. Cathepsin S was a less efficient activating enzyme. Cathepsin B and rhDPPI did not activate pro-rhDPPI, and the proenzyme was incapable of autoactivation. Incubation of both pro-rhDPPI and rhDPPI with cathepsin D resulted in degradation. Cystatin C and stefins A and B inhibited rhDPPI with K(i) values in the nanomolar range (K(i) = 0.5-1.1 nM). The results suggest that cathepsin L could be an important activator of DPPI in vivo and that cathepsin D and possibly the cystatins may contribute to DPPI downregulation.

Amino Acid Sequence↗

PubMed2001

Combustion of gasolines in premixed laminar flames European certified and California phase 2 reformulated gasoline.

Two gasoline qualities, European unleaded certified gasoline (EUCG) and California phase 2 reformulated gasoline (P2 RFG), were analysed. EUCG contained about twice the amount of alkyl benzenes compared to P2 RFG and a large amount of cyclohexane. As a balance, P2 RFG contained higher amounts of isooctane and MTBE. The gasolines were burned in a premixed laminar flame burner at 1 atm and at about stoichiometric fuel/air ratio. The species profiles were measured using on-line GC/MS. About 40 compounds were be detected in the gasoline flames. The EUCG resulted in formation of more reactive and toxic compounds. The combustion profiles of the fuel components showed a similar slope, which suggests that the fuel components burn quite independently of each other. Ethene and propene were the dominating species produced from the two gasolines. Commonly, substantial amounts of higher alkenes were found. Combustion of P2 RFG produced higher amounts of isobutene, propene, propyne, propadiene and methanol compared to combustion of EUCG. The high amount of isobutene is reasonably a result of high concentration of isooctane and MTBE in the fuel. The high amount of methanol formed is probably due to the MTBE present in the gasoline. EUCG produced significantly higher amounts of 1,3-butadiene, which quite likely is formed from the cyclohexane in the fuel. The benzene profiles from both gasolines shows an almost constant level up to 800 microm from the burner surface; this is probably due to formation of benzene from alkyl benzenes.

Air Pollutants↗

PubMed2001

Fast track as a routine for open heart surgery.

OBJECTIVE: Evaluation of thoracic epidural analgesia (TEA), normothermic cardiopulmonary bypass (CPB) and normothermic blood cardioplegia as a routine procedure for fast track open heart surgery. METHODS: Consecutive patients (n=250, age 36--81 years, mean 63, M/F, ratio=4) were subjected to the combination of general anaesthesia using ultra-short acting opiates, TEA, normothermic CBP, normothermic whole blood cardioplegia. Operative procedures included coronary artery bypass grafting (CABG), valve replacement, combined CABG and valves, aortic aneurysm and Maze III. LVEF ranged 20--76%. Eighty percent were in Tuman score 0--5 and 20% in score >5. RESULTS: All patients were extubated within 10 min after skin closure. There was one myocardial infarction. Four percent were shortly treated with cathecholamines. Postoperative atrial fibrillation was noticed in 9.6%. Four transient cerebral ischemic events were encountered. No neurological disturbance related to the use of TEA was seen. Seven patients were reoperated because of bleeding. Blood transfusion was given to 6.4% of the patients. Mortality was 0.8%. CONCLUSIONS: The combined methods provides a way for routine immediate postoperative extubation, with low morbidity and short hospital stay.

Adult↗

PubMed2001

Augmented intestinal trefoil factor (TFF3) and loss of pS2 (TFF1) expression precedes metaplastic differentiation of gastric epithelium.

The trefoil peptides spasmolytic polypeptide (SP), intestinal trefoil factor (ITF), and pS2 show lineage-specific expression in the normal gut and are strongly induced after mucosal injury. We assessed the relationship between this induction and the development of the regenerative epithelial lineage over time in the rat stomach and verified these observations in the metaplastic and dysplastic human stomach. Antral or colonic ulcers were induced in Wistar rats by application of serosal acetic acid and tissues harvested 2 hours to 125 days later. Human endoscopic biopsies or gastric resection specimens were also assessed. Tissues were examined by radioimmunoassay, immunoblotting, or immunohistochemistry for ITF, SP, and transforming growth factor alpha (rat) or ITF and pS2 (human) expression. ITF and SP mRNA in antral ulcer margins was localized by in situ hybridization. ITF and SP peptide expression rose steadily in ulcer margins after 4 days, with the rise in ITF being more pronounced. By 40 days, several hundred-fold elevations in ITF levels were present, with a field effect in uninvolved mucosa. Hyperproliferative, elongated glands of undifferentiated cells expressing abundant trefoil peptides and acid sulfomucins were present after day 12 and persisted after ulcer healing. ITF mRNA was aberrantly expressed in basal and mid-regions of these regenerative glands. In contrast, transforming growth factor alpha peptide expression rose promptly after injury then fell to baseline levels with healing. Seven months after injury, gastric atrophy, intestinal metaplasia, and severe dysplasia with conserved ITF expression were seen. ITF was also induced in human intestinal metaplasia and conserved in all gastric cancers, whereas expression of the gastric peptide pS2 was progressively reduced in the progression from metaplasia to dysplasia. Persistent, selective overexpression of ITF, possibly acting in an autocrine fashion, is a feature of regeneration after antral ulceration, and may provide insight into the nature of metaplastic phenotypes arising from chronic gastric injury. The loss of pS2 expression in metaplasia and cancer supports a role for this protein in gastric tumor suppression.

Adenocarcinoma↗

PubMed2001

Transoesophageal echocardiographic monitoring during paediatric cardiac surgery: obtainable information and feasibility in 532 children.

BACKGROUND: We hypothesized that transoesophageal echocardiography (TOE) performed by the anaesthesiologists would be beneficial for monitoring purposes during paediatric cardiac surgery. We present the results for the first 5 years in 532 consecutive children. METHODS: The probe was successfully inserted in 99% of cases and remained in the oesophagus for 211 min on average (range 10-555 min). RESULTS: Insignificant valve leak, single- or biventricular failure and volume depletion were the most common new findings due to TOE. Changes in inotropic strategy and volume replacement were the most frequent interventions. In 45% of the cases, new information was disclosed and, in a total of 8% of cases, decisive information was provided. Except for tracheal extubation in one child who was uneventfully reintubated, no severe complications were identified. CONCLUSIONS: These data stress the safety and ease of performing TOE in children undergoing cardiac surgery. There is evidence for benefit from TOE findings to potentially enhance the therapeutic basis.

Adolescent↗

PubMed2001

A 20-year study of an adolescent psychiatric clientele, with special reference to the age of onset.

During a period of 20 years (1968-1988) all inpatients admitted for the first time to the adolescent psychiatric unit in Copenhagen (n = 841) were classified in accordance with social and psychiatric variables, to describe the clientele as a group and, furthermore, to investigate changes occurring during that period. The total clientele had a broad age range (12-21 years), with as many as 36% less than 15 years old. Eleven percent of the patients had attempted suicide before admission. Fifty-six percent of the total group were diagnosed as psychotic or as borderline cases. The patients came predominantly from lower social levels, and almost half the group had a child debut defined as symptoms that had resulted in referral for further investigation during childhood. Moreover, among the schizophrenic patients 35% had an early onset. The age of onset may have some clinical significance, as this item was related to several sociodemographic variables. Finally, an increase in the rate of psychoses and lower social class was recorded during the period.

Adolescent↗

PubMed2001

A 10-year follow-up study of an adolescent psychiatric clientele and early predictors of readmission.

Over a period of 20 years (from 1968 to 1988) all inpatients (n = 839) who were admitted for the first time to the adolescent psychiatric unit in Copenhagen were registered, and 40 social and psychiatric variables were recorded, to investigate early predictors of later readmission. Overall, 44.8% of the patients were readmitted within a certain observation period (range, 1.5-21.5 years). Among a subsample of 488 patients (58%) who could be followed up for more than 10 years after their first admission 26% became heavy users of psychiatric services, defined as long-term inpatients or revolving-door patients. Severe early diagnoses (schizophrenia and affective psychoses) were strongly associated with rapid relapses and frequent readmissions. A statistical estimate of the risk of later heavy use based on 12 independent variables is presented.

Adolescent↗

PubMed2001

A specific PCR assay for the dermatophyte fungus Microsporum canis.

A DNA fragment of approximately 1.2 kb, generated from the common dermatophyte Microsporum canis by arbitrarily primed polymerase chain reaction (PCR) using random primer OPU13, was cloned and sequenced. Based on the resulting sequencing data, a forward primer (MC1F) and a reverse primer (MC1R) have been designed and assessed by PCR for their usefulness in the improved identification of M. canis. The results obtained suggest that these primers are specific for M. canis, as a band of 900 bp was amplified in PCR with genomic DNA from M. canis only, and not from any of the other dermatophyte species or varieties, other fungi or common bacteria examined. Combining this PCR technique with a rapid mini-preparation method for fungal DNA, a definitive diagnosis of M. canis can be achieved within a day from the primary cultures. Future refinement of a DNA purification protocol from clinical specimens would further enhance the potential of the PCR based test for improved detection and identification of M. canis.

DNA, Fungal↗

PubMed2001

Tissue injury and the inflammatory response to pediatric cardiac surgery with cardiopulmonary bypass: a descriptive study.

BACKGROUND: There are few detailed descriptions of the inflammatory response to cardiac surgery with cardiopulmonary bypass (CPB) in children beyond 24 h postoperatively. This is especially true for the antiinflammatory cytokines and the extent of tissue injury. The aim of the current study was to describe the inflammatory and injury responses in uncomplicated pediatric cardiac surgery with CPB, where methylprednisolone and modified ultrafiltration (MUF) were used. METHODS: Blood samples were collected up to 48 h postoperatively. Cytokines (tumor necrosis factor-alpha and interleukin-6, -1beta, -10, and -1ra), complement (C3d and C4d) and coagulation system (prothrombin activation fragments 1 and 2 and antithrombin III) activation, neutrophil elastase, and the resulting tissue injury (creatine kinase, lactate dehydrogenase, alanine transaminase, amylase, and gamma-glutamyl transferase) were measured. RESULTS: The proinflammatory cytokine release varied widely, in contrast to a clear-cut antiinflammatory response. Cytokine concentrations did not decrease immediately after MUF, and no rebound increases later in the postoperative period were observed. The coagulation system, but not complement, was activated. There was a late release of C-reactive protein. Tissue injury could be quantified biochemically without evidence of hepatic or pancreatic dysfunction. CONCLUSION: In this group of uncomplicated subjects, the antiinflammatory cytokine and tissue injury responses were well defined, in contrast to a variable proinflammatory cytokine release. This was accompanied by activation of the coagulation system but not of complement. Concentrations of inflammatory mediators did not decrease immediately after MUF, and there was no evidence for rebound release later in the postoperative period.

Blood Coagulation↗

PubMed2001

Increased platelet reactivity and significant changes in coagulation markers after cavopulmonary connection.

OBJECTIVE: To evaluate platelet reactivity and coagulation markers after surgical palliation of univentricular hearts. DESIGN AND PATIENTS: Cross sectional survey of 24 patients, median age 11 (range 4-22) years, at 2 (range 0.5-6) years after a total cavopulmonary connection (TCPC; n = 14) or a bidirectional Glenn anastomosis (Glenn; n = 10). MAIN OUTCOME MEASURES: Platelet reactivity and/or coagulation markers were measured in 20 patients (four excluded because of anticoagulant treatment) and compared with 33 healthy controls, median age 12 (range 6-16) years. RESULTS: None of the patients had clinically apparent thromboembolic events. However, increased platelet reactivity was observed ex vivo both after collagen induced platelet aggregation (median 73% (interquartile range 61-84%) in patients, and 61% (47-69%) in controls; p < 0.01), and after ADP induced platelet aggregation (69% (53-77%) in patients, and 56% (40-66%) in controls; p < 0.05). Concentrations of protein S antigen, antithrombin III, and protein C activity were reduced after both TCPC and Glenn. A concomitant decrease was seen in coagulation factor II, VII, X, and factor VII clot activity. CONCLUSIONS: Several abnormalities in the coagulation system were observed after bidirectional Glenn anastomosis, similar to alterations previously described in Fontan operated and TCPC patients. Antithrombotic treatment in these patients is still an unresolved issue, but aspirin is often recommended. This study shows that such a strategy is rational and the results suggest that antiplatelet treatment may be advantageous, either alone or in combination with oral anticoagulant treatment.

Adolescent↗

PubMed2001

Elevated androgens and prolactin in aromatase-deficient mice cause enlargement, but not malignancy, of the prostate gland.

Although androgens are the main steroids controlling the growth of the mammalian prostate, increasing evidence demonstrates that estrogens also regulate prostate development and growth. This study describes the effects of estrogen deficiency using aromatase knockout mice (ArKO) with targeted disruption of the cyp19 gene. Serum and tissue testosterone and 5alpha-dihydrotestosterone as well as serum PRL levels are significantly (P < 0.05) elevated in mature male ArKO mice. Histological, stereological, and immunohistochemical studies demonstrated enlargement of the ventral, anterior, and dorsolateral lobes of the prostate in young and older ArKO mice. Hyperplasia of the epithelial, interstitial, and luminal compartments was identified and associated with up-regulation of androgen receptors. There was no evidence of malignancy as the animals aged (up to 56 weeks). The changes observed in the prostates of ArKO mice were unaffected by maintaining mice on regular or soy-free diets. It is concluded in ArKO mice that, despite the long-term elevation of androgens and PRL, the absence of estrogen in these animals does not result in induction of malignancy in the prostate gland.

Androgens↗

PubMed2000

Mapping of the locus for cholestasis-lymphedema syndrome (Aagenaes syndrome) to a 6.6-cM interval on chromosome 15q.

Patients with cholestasis-lymphedema syndrome (CLS) suffer severe neonatal cholestasis that usually lessens during early childhood and becomes episodic; they also develop chronic severe lymphedema. The genetic cause of CLS is unknown. We performed a genome screen, using DNA from eight Norwegian patients with CLS and from seven unaffected relatives, all from an extended pedigree. Regions potentially shared identical by descent in patients were further characterized in a larger set of Norwegian patients. The patients manifest extensive allele and haplotype sharing over the 6.6-cM D15S979-D15S652 region: 30 (83.3%) of 36 chromosomes of affected individuals carry a six-marker haplotype not found on any of the 32 nontransmitted parental chromosomes. All Norwegian patients with CLS are likely homozygous for the same disease mutation, inherited from a shared ancestor.

Alleles↗

PubMed2000

Carica papaya glutamine cyclotransferase belongs to a novel plant enzyme subfamily: cloning and characterization of the recombinant enzyme.

A full-length cDNA encoding Carica papaya glutamine cyclotransferase was cloned by RT-PCR on the basis of results from amino acid sequencing of tryptic fragments of the native enzyme. The cDNA of 1036 nucleotides encodes a typical 22-residue signal peptide and a mature protein of 266 residues with a calculated molecular mass of 30,923 Da. Five plant ESTs encoding putative QCs highly homologous to PQC were identified and the numbers and locations of cysteines and N-glycosylation sites are conserved. The plant QC amino acid sequences are very different from the known mammalian QC sequences and no clear homology was observed. The PQC cDNA was expressed in Escherichia coli as either His-tagged PQC, with three different signal peptides and in fusions with thioredoxin, glutathione S-transferase, and (pre-) maltose-binding protein. In all cases, the expressed protein was either undetectable or insoluble. Expression in Pichia pastoris of PQC fused to the alpha-factor leader resulted in low levels of PQC activity. Extracellular expression of PQC in the insect cell/baculovirus system was successful and 15-50 mg/liter of active PQCs with three different secretion signals was expressed and purified. Further, PQC N-terminally fused to a combined secretion signal/His-tag peptide was correctly processed by the host signal peptidase and the His-tag could subsequently be removed with dipeptidyl peptidase I. The expressed products were characterized by activity assays, SDS-PAGE, N-terminal amino acid sequencing, MALDI-TOF mass spectroscopy, and peptide mass fingerprint analysis.

Amino Acid Sequence↗

PubMed2000

Position sense testing: influence of starting position and type of displacement.

OBJECTIVE: To assess the effect of starting position, target position, and various types of limb displacement on repositioning tests commonly used for clinical evaluation of rehabilitation. SETTING: Controlled laboratory environment. PARTICIPANTS: Sixteen healthy volunteer subjects. MAIN OUTCOME MEASURE: Absolute error, ie, the absolute difference between target and replicate positions. DESIGN: Each subject performed four testing procedures consisting of different types of limb displacement (active, passive, and passive during antagonist muscle contraction). For each procedure, horizontal movements were performed ipsilaterally about the right glenohumeral joint from one intermediate starting position (40 degrees ) and two extreme starting positions (0 degrees and 80 degrees ). Four fixed target positions (16 degrees , 32 degrees, 48 degrees , 64 degrees ) were presented for each starting position. The subjects were required to replicate target position after returning to the respective starting position. RESULTS: Lower repositioning errors occurred with active displacement procedures compared with passive, and with the intermediate starting position compared with the extreme. Target position, however, had no effect on repositioning errors. CONCLUSIONS: Starting position and type of displacement should be considered in interpretations and comparisons of data from clinical studies.

Adult↗

PubMed2000

Determinants of infant and child mortality in the West Bank and Gaza Strip.

Infant and child mortality in the West Bank and Gaza Strip has steadily reduced since 1967, even though fertility has remained extremely high. In this paper the determinants of infant and child mortality are discussed, with particular emphasis on the role of consanguineous marriages, short birth spacing and maternal education. It is shown that short birth spacings and type of marriage are more important determinants of infant mortality than maternal education. Moreover, the relative role of consanguineous marriages appears to increase with time.

Adolescent↗

PubMed2000

Application of PCR to the identification of dermatophyte fungi.

Infection of the keratinised tissues (skin, hair and nails) in man and animals by keratinophilic fungi (dermatophytes) results in dermatophytosis (also known as tinea or ringworm). As conventional laboratory procedures for the identification of dermatophytes are either slow or lack specificity, improved diagnostic methods are required. The application of nucleic acid amplification technology has made rapid and precise identification of dermatophytes possible. Recent studies have shown that when one of the four random primers (OPAA11, OPD18, OPAA17 and OPU15) was used in arbitrarily primed PCR (AP-PCR), up to 20 of the 25 dermatophyte species or subspecies under investigation could be distinguished on the basis of characteristic band patterns detected in agarose gel electrophoresis. A combination of two random primers (OPD18 and OPAA17) used in separate reaction tubes identified 23 of the 25 dermatophyte species or subspecies examined. AP-PCR provides a rapid and practical tool for identification of dermatophyte isolates that is independent of morphological and biochemical characteristics and thus enhances laboratory diagnosis of dermatophytosis.

Animals↗

PubMed2000

Elevated intramuscular concentration of bradykinin in jaw muscle increases the fusimotor drive to neck muscles in the cat.

Patients suffering from temporomandibular dysfunction exhibit clinical findings such as fatigue, painful muscles, and muscles that are tender to palpation, not only in the temporomandibular area, but also in the neck/shoulder region. The mechanisms behind this are not known, although previous studies of similar spreading phenomena have revealed a possible involvement of the fusimotor system. In the present study, we evaluated the activity of this system by recording the activity of muscle spindle afferents from dorsal neck muscles after intramuscular injections of 6 microg to 25 microg bradykinin in the ipsilateral masseter muscle. A total of 23 muscle spindle afferents from the trapezius and splenius muscles was recorded at the C3-C4 level in 7 adult cats anesthetized with alpha-chloralose. Of these 23 afferents, 17 (74%) showed significantly different responses to bradykinin injections compared with control injections (dissolving agent, Tyrode), and the majority of the effects were compatible with an increased static fusimotor drive to the muscle spindle system. Thus, the results demonstrate potent reflex connections from groups III and IV masseter muscle afferents to fusimotor neurones on the C3-C4 level. It is concluded that the fusimotor system might play a significant role in the mechanisms behind the spread of muscle pain and tension from the temporomandibular region to the neck.

Afferent Pathways↗

PubMed2000

Localization of activin beta(A)-, beta(B)-, and beta(C)-subunits in humanprostate and evidence for formation of new activin heterodimers of beta(C)-subunit.

Activin ligands are formed by dimerization of activin ss(A)- and/or ss(B)-subunits to produce activins A, AB, or B. These ligands are members of the transforming growth factor-ss superfamily and act as growth and differentiation factors in many cells and tissues. New additions to this family include activin ss(C)-, ss(D)-, and ss(E)-subunits. The aim of this investigation was to examine the localization of and dimerization among activin subunits; the results demonstrate that activin ss(C) can form dimers with activin ss(A) and ss(B) in vitro, but not with the inhibin alpha-subunit. Using a specific antibody, activin ss(C) protein was localized to human liver and prostate and colocalized with ss(A)- and ss(B)-subunits to specific cell types in benign and malignant prostate tissues. Activin C did not alter DNA synthesis of the prostate tumor cell line, LNCaP, or the liver tumor cell line, HepG2, in vitro when added alone or with activin A. Therefore, the capacity to form novel activin heterodimers (but not inhibin C) resides in the human liver and prostate. Activin A, AB, and B have diverse actions in many tissues, including liver and prostate, but there is no known biological activity for activin C. Thus, the evidence of formation of activin AC or BC heterodimers may have significant implications in the regulation of levels and/or biological activity of other activins in these tissues.

Activins↗