PubMed Health⌕ Search

Biomedical subjects

C Lauritzen

Publications and source records attributed to C Lauritzen.

At least 19 recordsLinked to original sources
PubMed2004

Advances in craniosynostosis research and management.

The purpose of the present paper is to analyze the most recent advances in the field of craniosynostosis basic and clinical research and management, and to give an overview of the more frequently adopted surgical strategies. After reviewing some basic concepts regarding normal craniofacial embryology and growth, aetiopathogenesis of craniosynostosis and craniofacial dysostosis, classification and diagnosis and historical evolution of surgical treatment, the authors elaborate on a selection of topics that have modified our current understanding of and therapeutical approach to these disease processes. Areas covered include advances in molecular biology and genetics, imaging techniques and surgical planning, resorbable fixation technology, bone substitutes and tissue engineering, distraction osteogenesis and the spring-mediated cranioplasties, resorbable distractor devices, minimally invasive surgery and in utero surgery. A review of the main subtypes of craniosynostosis and craniofacial dysostosis is presented, including their specific clinical features and a commentary on the presently available surgical options.

Craniosynostoses↗
PubMed2003

Craniofacial surgery over 30 years in Göteborg.

Craniofacial surgery is a new sub-specialty in the field of plastic reconstructive surgery and is dedicated to the treatment of severe cranial and facial malformations. Craniofacial surgery gradually started in Göteborg in the late 1970's and has been acting as the Scandinavian center since 1983. Over these 30 years an almost complete change in surgical techniques has evolved. Also profound changes in timing of surgery have followed. Results have been dramatically improved based on critical evaluation of standardized registration of long-term results. One of the most dramatic developments has been the introduction of implantable stainless steel springs. This has changed the treatment of Craniosynostosis completely and has made midfacial advancement procedures possible without relapse.

Craniofacial Abnormalities↗
PubMed2001

Structure of human dipeptidyl peptidase I (cathepsin C): exclusion domain added to an endopeptidase framework creates the machine for activation of granular serine proteases.

Dipeptidyl peptidase I (DPPI) or cathepsin C is the physiological activator of groups of serine proteases from immune and inflammatory cells vital for defense of an organism. The structure presented shows how an additional domain transforms the framework of a papain-like endopeptidase into a robust oligomeric protease-processing enzyme. The tetrahedral arrangement of the active sites exposed to solvent allows approach of proteins in their native state; the massive body of the exclusion domain fastened within the tetrahedral framework excludes approach of a polypeptide chain apart from its termini; and the carboxylic group of Asp1 positions the N-terminal amino group of the substrate. Based on a structural comparison and interactions within the active site cleft, it is suggested that the exclusion domain originates from a metallo-protease inhibitor. The location of missense mutations, characterized in people suffering from Haim-Munk and Papillon-Lefevre syndromes, suggests how they disrupt the fold and function of the enzyme.

Amino Acid Sequence↗
PubMed2001

Tetrameric dipeptidyl peptidase I directs substrate specificity by use of the residual pro-part domain.

The crystal structure of mature dipeptidyl peptidase I reveals insight into the unique tetrameric structure, substrate binding and activation of this atypical papain family peptidase. Each subunit is composed of three peptides. The heavy and light chains form the catalytic domain, which adopts the papain fold. The residual pro-part forms a beta-barrel with the carboxylate group of Asp1 pointing towards the substrate amino-terminus. The tetrameric structure appears to stabilize the association of the two domains and encloses a 12700 A3 spherical cavity. The tetramer contains six chloride ions, one buried in each S2 pocket and two at subunit interfaces.

Animals↗
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

Expander elements in craniofacial surgery: an experimental study in rabbits.

With the inception of craniofacial surgery elaborate surgical procedures were introduced for the treatment of craniosynostosis. Recently the use of implantable springs to aid simple strip craniectomies for these conditions has been described. Having shown the feasibility of using springs for dynamic skull reshaping, several questions remain to be answered, all of them about how to control the spring action clinically. One of the most important questions concerns force. The purpose of this study was to evaluate experimentally the effect of two springs of different strengths on the growth of rabbit calvaria after strip craniectomy. Thirty-two 6-week-old rabbits were randomised into one of four groups: sham-operation where only amalgam markers were inserted after subperiostal dissection; strip craniectomy of the sagittal suture, no expansion; strip craniectomy of the sagittal suture and insertion of an expander element made of titanium molybdenum alloy (TMA); and strip craniectomy sagittal suture and insertion of an expander element made of stainless steel (SS). SS springs delivered a range of forces from 2.42-2.18 N, whereas the TMA expander elements delivered a range from 1.39-1.09 N. The parietal bone marker separation after 12 weeks was 4.9 mm in the TMA group and 7.4 mm in the SS group. This resulted in a significant increase of the calvarian height compared with control groups. Histological examination showed intramembranous bone formation in the bone gap in all groups.

Animals↗
PubMed2001

Long-term follow-up of dynamic cranioplasty for brachycephaly--non-syndromal bicoronal synostosis.

We followed up 10 patients whose non-syndromal bicoronal synostosis had been operated on with a dynamic cranioplasty technique developed by this craniofacial unit in 1992. With this technique, the growth of the brain is redirected in an anteroposterior direction as wire-mediated compression and restraint are exerted on the transverse and vertical dimensions of the skull. The mean operating time was 160 minutes (range 120-275) and mean stay in the intensive care unit was 36 hours (range 23-58). There was no operative mortality and few complications. The surgical results were assessed objectively by analysis of cephalometric tracings. The mean (SD) cephalic index was 87.6 (4.9) preoperatively and 77.7 (1.8) postoperatively (p = 0.001). The modified Whitaker scale was used as a subjective outcome measurement, and nine patients were classified as Whitaker grade 1 (no additional surgery). One patient required additional intracranial surgery. A questionnaire was sent to all families to obtain an additional subjective measurement of outcome. Parents' satisfaction was high. We conclude that dynamic cranioplasty is a safe and efficient operation for treatment of brachycephaly.

Cephalometry↗
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

[Gynecological problems of the aging woman].

The increasing number of old aged women requires the establishment of geriatric gynecology as a new subspecialty of our profession. The care of senior women in the gynecologists office should not be limited to the conventional gynecological diseases. These are of course dealt with in this paper; however should also be included, in a new understanding and broadening of our specialty, the women-specific diseases of old age. These extragenital diseases are therefore also touched upon. This extension of gynecology follows logically from the broad spectrum of effects of the female sexual hormones in the hands of the gynecologists and especially of long-term estrogen substitution into many neighbour medical specialties, like internal medicine, orthopedics, psychiatry and others. The gynecologist must have a working knowledge of these women-diseases including their physiopathology, differential diagnosis, treatment and, above all, prevention. The new understanding is moreover based upon the unique position of the gynecologist in the regular prevention and last, not least, upon the special confidence of the clients to their women-doctor and upon the special human intimacy in the relation between female patients and gynecologists. The care of senior women today includes life style counseling with the aim of prevention of preventable diseases. Also these points of view are touched upon. Medicine, which has given thirty additional years to the life of women, has also to take the responsibility to preserve physical and mental wellness through this segment of existence in good life quality saving the seniors from suffering of the preventable diseases of old age.

Aged↗
PubMed2000

Evaluation of a surgical technique for trigonocephaly.

Clinically diagnosed trigonocephaly have been treated by a standard surgical technique developed at Göteborg University Craniofacial Unit. To evaluate the technique we designed a study to include both subjective and objective assessments. Of 30 patients operated on between 1988-1997, 15 patients with at least three years postoperative follow-up have been included. An evaluation of the surgical outcome of the bitemporal width, the forehead contour, and the intercanthal distance was made both subjectively using a visual analogue scale (VAS) and objectively with analyses of cephalograms taken preoperatively and postoperatively at 3 and 5 years of age. For the subjective evaluation a control group of 10 randomly selected children from a Child Welfare Centre were selected. For the objective evaluation the control group consisted of cephalograms from children born with cleft lip and palate who were matched regarding sex and age. Both cephalometric analysis and subjective studies of the outcome indicated improvement. When the forehead contour was investigated the number of patients who had been improved or corrected completely was higher when evaluated subjectively. When interorbital distance on cephalograms and intercanthal distance scores on VAS were evaluated, again the subjective study indicated improvement in more subjects.

Cephalometry↗
PubMed1999

[Assymetric skull? Early correct diagnosis is a must! Positional skull deformities can be avoided].

During the past few years the supine sleeping position has successfully been reintroduced for infants in order to prevent sudden infant death syndrome. However, the change in sleeping position has not been accompanied by a soft pillow under the infants head, which has probably caused a higher incidence of acquired skull deformities. These positional skull deformities need to be prevented or treated.

Craniosynostoses↗
PubMed1999

Removal of N-terminal polyhistidine tags from recombinant proteins using engineered aminopeptidases.

We have developed a specific and efficient method for complete removal of polyhistidine purification tags (HisTags) from the N-termini of target proteins. The method is based on the use of the aminopeptidase dipeptidyl peptidase I (DPPI), either alone or in combination with glutamine cyclotransferase (GCT) and pyroglutamyl aminopeptidase (PGAP). In both cases, the HisTag is cleaved off by DPPI, which catalyzes a stepwise excision of a wide range of dipeptides from the N-terminus of a peptide chain. Some sequences, however, are resistant to DPPI cleavage and a number of mature proteins have nonsubstrate N-termini which protects them against digestion. For such proteins, HisTags composed of an even number of residues can be cleaved off by treatment with DPPI alone. When the target protein is unprotected against DPPI, a blocking group is generated enzymatically from a glutamine residue inserted between the HisTag and the target protein. A protein with a HisTag-Gln extension is incubated with both DPPI and GCT. As above, the polyhistidine sequence is cleaved off by DPPI, but when the glutamine residue appears in the N-terminus, it is immediately converted into a pyroglutamyl residue by an excess of GCT and further DPPI digestion is prevented. The desired sequence is finally obtained by excision of the pyroglutamyl residue with PGAP. All the enzymes employed can bind to immobilized metal affinity chromatography (IMAC) matrices, and in this paper we demonstrate a simple and highly effective process combining IMAC purification of His-tagged proteins, our aminopeptidase-based method for specific excision of HisTags and use of subtractive IMAC for removing processing enzymes. Typical recoveries were 75-90% for the enzymatic processing and subtractive IMAC. The integrated process holds promises for use in large-scale production of pharmaceutical proteins because of a simple overall design, use of robust and inexpensive matrices, and use of enzymes of either recombinant or plant origin.

Amino Acid Sequence↗