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Biomedical subjects

P K Jensen

Publications and source records attributed to P K Jensen.

At least 19 recordsLinked to original sources
PubMed1999

Probing proteomes using capillary isoelectric focusing-electrospray ionization Fourier transform ion cyclotron resonance mass spectrometry.

Unlike the genome, the proteome is exquisitely sensitive to cellular conditions and will consist of proteins having abundances dependent upon stage in the cell cycle, cell differentiation, response to environmental conditions (nutrients, temperature, stress etc.), or disease state(s). Therefore, the study of proteomes under well-defined conditions can provide a better understanding of complex biological processes and inference of protein function. Thus, much faster, more sensitive, and precise capabilities for the characterization of cellular constituents are desired. We describe progress in the development and initial application of the powerful combination of capillary isoelectric focusing (CIEF) and Fourier transform ion cyclotron resonance (FTICR) mass spectrometry for measurements of the proteome of the model system Escherichia coli. Isotope depletion of the growth media has been used to improve mass measurement accuracy, and the comparison of CIEF-FTICR results for the analysis of cell lysates harvested from E. coli cultured in normal and isotopically depleted media are presented. The initial studies have revealed 400-1000 putative proteins in the mass range 2-100 kDa from total injections of approximately 300 ng of E. coli proteins in a single CIEF-FTICR analysis.

Bacterial Proteins↗
PubMed1999

Resolution of retinal digital colour images.

Several digital colour cameras commercially available were fitted on a fundus camera. A test target placed in an artificial eye was used for measurements of the resolution of the resulting digital images and compared to film material. The maximal target resolution of the fundus camera was 6 microm corresponding to 24 microm at the image plane. The best film material matched this closely. To avoid aliasing, the size of the digital image must be 2-3000 pixels to match this resolution. This criterium is fulfilled by present high-end digital cameras. Further development of hardware and software is needed for their introduction into clinical settings.

Color↗
PubMed1999

Leiomyoma of the ciliary body. Report of 2 cases.

PURPOSE AND METHODS: The files of the Eye Pathology Institute contain only two cases of leiomyoma of the ciliary body. The diagnoses were re-evaluated, applying modern immunostainings. RESULTS: The tumors were composed of interlacing fascicles of spindle-shaped cells with bright eosinophilic cytoplasm and cigar-shaped nuclei. Both tumors were well-vascularized, mostly by thin, branching capillaries. Larger vessels were also seen. In one case the tumor perforated the sclera. The tumor cells reacted with the reticulum stain and the Masson trichrome and were positive for antibodies against: smooth muscle actin (SMA), muscle specific actin (MSA), laminin and vimentin (one case). CONCLUSION: Leiomyoma of the ciliary body is a rare smooth muscle cell tumor that may arise from either pericytes, ciliary - or intrascleral heterotopic muscle.

Actins↗
PubMed1999

Molecular cytogenetic detection of 9q34 breakpoints associated with nail patella syndrome.

The nail patella syndrome (NPS1) is an autosomal dominant disorder characterised by dysplasia of the finger nails and skeletal abnormalities. NPS1 has been mapped to 9q34, to a 1 cM interval between D9S315 and the adenylate kinase gene (AK1). We have mapped the breakpoints within the candidate NPS1 region in two unrelated patients with balanced translocations. One patient [46,XY,t(1;9)(q32.1;q34)] was detected during a systematic survey of old cytogenetic files in Denmark and southern Sweden. The other patient [46,XY,t(9;17)(q34.1;q25)] was reported previously. D9S315 and AK1 were used to isolate YACs, from which endclones were used to isolate PACs. Two overlapping PAC clones span the 9q34 breakpoints in both patients, suggesting that NPS1 is caused by haploinsufficiency due to truncation or otherwise inactivation of a gene at or in the vicinity of the breakpoints.

Chromosome Fragility↗
PubMed1999

Identification of novel and known mutations in the genes for keratin 5 and 14 in Danish patients with epidermolysis bullosa simplex: correlation between genotype and phenotype.

Epidermolysis bullosa simplex (EBS) is a group of autosomal dominant inherited skin diseases caused by mutations in either the keratin 5 (K5) or the keratin 14 (K14) genes and characterized by development of intraepidermal skin blisters. The three major subtypes of EBS are Weber-Cockayne, Koebner, and Dowling-Meara, of which the Dowling-Meara form is the most severe. We have investigated five large Danish families with EBS and two sporadic patients with the Dowling-Meara form of EBS. In the sporadic Dowling-Meara EBS patients, a novel K14 mutation (N123S) and a previously published K5 mutation (N176S) were identified, respectively. A novel K14 mutation (K116N) was found in three seemingly unrelated families, whereas another family harbored a different novel K14 mutation (L143P). The last family harbored a novel K5 mutation (L325P). The identified mutations were not present in more than 100 normal chromosomes. Six polymorphisms were identified in the K14 gene and their frequencies were determined in normal controls. These polymorphisms were used to show that the K14 K116N mutation was located in chromosomes with the same haplotype in all three families, suggesting a common ancestor. We observed a strict genotype-phenotype correlation in the investigated patients as the same mutation always resulted in a similar phenotype in all individuals with the mutation, but our results also show that it is not possible to predict the EBS phenotype merely by the location (i.e., head, rod, or linker domains) of a mutation. The nature of the amino acid substitution must also be taken into account.

Denmark↗
PubMed1999

Evidence that mutations in the X-linked DDP gene cause incompletely penetrant and variable skewed X inactivation.

X chromosome inactivation results in the random transcriptional silencing of one of the two X chromosomes early in female development. After random inactivation, certain deleterious X-linked mutations can create a selective disadvantage for cells in which the mutation is on the active X chromosome, leading to X inactivation patterns with the mutation on the inactive X chromosome in nearly 100% of the individual's cells. In contrast to the homogeneous patterns of complete skewed inactivation noted for many X-linked disorders, here we describe a family segregating a mutation in the dystonia-deafness peptide (DDP) gene, in which female carriers show incompletely penetrant and variable X inactivation patterns in peripheral blood leukocytes, ranging between 50:50 and >95:5. To address the genetic basis for the unusual pattern of skewing in this family, we first mapped the locus responsible for the variable skewing to the proximal long arm (Xq12-q22) of the X chromosome (Z=5. 7, P=.002, LOD score 3.57), a region that includes both the DDP and the XIST genes. Examination of multiple cell types from women carrying a DDP mutation and of peripheral blood leukocytes from women from two unrelated families who carry different mutations in the DDP gene suggests that the skewed X inactivation is the result of selection against cells containing the mutant DDP gene on the active X chromosome, although skewing is apparently not as severe as that seen for many other deleterious X-linked mutations. Thus, DDP is an example of an X-linked gene for which mutations cause partial cell selection and thus incompletely skewed X inactivation in peripheral blood leukocytes.

Adult↗
PubMed1999

Long-term outcome of knee and ankle injuries in elite football.

To estimate the risk and evaluate the long-term outcome of knee and ankle injuries in former national team elite football, 69 players were randomly selected, followed by clinical and stress radiographic examinations. Thirty-nine players (49 knees) had had knee injuries and 29 ankle injuries (35 ankles). The median time from injury until study examination was 25 years. The knee injuries were tears of the medial collateral ligament (MCL) in 24 cases combined with rupture of the anterior cruciate ligament (ACL) and meniscus lesions in three. Meniscus lesions had occurred in 17 cases including three combined with ACL and MCL and another two with ACL ruptures. Isolated rupture of the ACL had occurred in four cases. The ankle lesions were in 26 of 35 cases ruptures of the lateral ligaments. In all, 12 players had completely stopped football and three had changed occupation. Signs of arthritis were present in 63% of the injured knees and in 33% of the injured ankles. The incidence of arthritis in the group of 17 uninjured players was 26% in the knee and 18% the ankle. In elite football players knee and ankle injuries seem to have a serious long-term outcome, but also uninjured players have a higher risk of developing arthritis than the normal population.

Adult↗
PubMed1999

Optic nerve oxygen tension in pigs and the effect of carbonic anhydrase inhibitors.

PURPOSE: To evaluate how the oxygen tension of the optic nerve (ONP(O)2) is affected by the administration of the carbonic anhydrase inhibitors dorzolamide and acetazolamide and by alterations in oxygen and carbon dioxide in the breathing mixture. METHODS: Polarographic oxygen electrodes were placed in the vitreous humor immediately over the optic disc in 20 anesthetized pigs. Blood gasses and cardiovascular physiology were monitored. ONP(O)2 was recorded continuously with breathing gasses of 21% O2-79% N2, 100% O2, 20% O2-80% N2, and 5.19% CO2-19.9%, O2-74.9% N2. Acetazolamide (15-1000 mg) and dorzolamide (6-1000 mg) were administered intravenously. RESULTS: The mean (+/- SD) ONP(O)2 was found to be 24.1+/-11.6 mm Hg when the pigs were breathing room air and 50.7+/-29.3 mm Hg when they were breathing 100% O2 (n = 15; P < 0.001). In response to breathing 5.19% CO2, ONP(O)2 changed from 20.8+/-5.6 mm Hg (with 20.0% O2) to 28.9+/-3.6 mm Hg (n = 4; P < 0.001). Intravenous injections of 500 mg dorzolamide increased ONP(O)2 from 16.4+/-6.1 mm Hg to 26.9+/-12.2 mm Hg, or 52.5%+/-21.2% (n = 5; P = 0.017). A dose-dependent effect on ONP(O)2 was seen with intravenous dorzolamide doses of 1000, 500, 250, 125, 63, 27, 15, and 6 mg. Intravenous injections of 500 mg acetazolamide increased ONP(O)2 from 23.6+/-9.5 mm Hg to 30.9+/-10.0 mm Hg (n = 6; P < 0.001), and a dose-dependent effect was seen with doses of 1000, 500, 250, 125, 31, and 15 mg. CONCLUSIONS: ONP(O)2 is significantly increased by the carbonic anhydrase inhibition of dorzolamide and acetazolamide, and the effect is dose dependent. These data demonstrate for the first time a direct effect of carbonic anhydrase inhibitors on ONP(O)2.

Acetazolamide↗
PubMed1998

Monitoring protein refolding induced by disulfide formation using capillary isoelectric focusing-electrospray ionization mass spectrometry.

Rapid growth in the biotechnology industry has led to a dramatic increase in attention to the protein folding problem. Understanding protein-folding pathways is essential to the production of biopharmaceuticals since commercial production of recombinant proteins often requires a protein-refolding process for recovery of high yields. Protein folding coupled to the formation of disulfide bonds presents one of the simplest approaches to studying folding intermediates. On-line capillary isoelectric focusing-electrospray ionization mass spectrometry (CIEF-ESIMS) is demonstrated for kinetic studies of disulfide bond-induced protein refolding. Refolding intermediates of bovine pancreatic ribonuclease A, a model system for this study, are blocked at different stages by alkylating free thiols with iodoacetate. The alkylation reaction results in the introduction of charge (-1) and mass (59) differences for each alkylation site, providing the means for predictable separation and direct identification of refolding intermediates using CIEF-ESIMS. Besides the observation of refolding intermediates containing different numbers of disulfide bonds and even mixed disulfides, the two-dimensional resolving power of CIEF-ESIMS allows the determination of conformational heterogeneity among groups of refolding intermediates.

Alkylation↗
PubMed1998

Necrosis of the femoral head after kidney transplantation.

We reviewed the medical records of 750 patients (445 men, 305 women), who had received a kidney transplant during the period 1968-1995, for any sign of necrosis of the femoral head. For post-operative immunosuppression, 374 patients had received high-dose corticosteroids (average 12.5 g during the first year post-operatively), while 376 patients had received low-dose corticosteroids (average 6.5 g during the first year post-operatively) and cyclosporin A. Survival curves according to Kaplan and Meier (J Am Stat Ass 1958: 53: 457-481) were constructed. In the high-dose steroid group, 42/374 patients (11.2%) developed femoral head necrosis, at an average of 26.2 months post-transplantation. In the low-dose steroid group, only 19/376 (5.1%) patients developed this complication, at an average of 20.5 months post-transplantation. This difference in numbers of femoral head necroses was highly significant (p < 0.005). We conclude that steroid doses should be minimized whenever feasible in post-transplant immunosuppression therapy.

Adolescent↗
PubMed1997

[Relevance of the 112-emergency calls among the clientele of the emergency department of the Herlev hospital admitting office].

It is a common view, shared by Emergency Department staff and ambulance crews, that a large number of patients unnecessarily use Emergency Service ambulances instead of transporting themselves to the hospital by other, more appropriate means. In this retrospective study, 528 consecutive Emergency Service calls to the Herlev Hospital Casualty/Emergency Department during a six week period were reviewed for relevance. Attention was solely aimed at the relevance of the use of Emergency Service ambulances in each case, but not on patient or health care providers' perception of urgency. All calls resulting in admission to hospital were pre-defined as being relevant. Seventeen point six percent of all calls were deemed irrelevant. Thirty-three percent of all calls not resulting in admission were deemed irrelevant. The results confirm Emergency Department health care providers' and ambulance crews' view that Emergency Service ambulances are used inappropriately by the public.

Ambulances↗
PubMed1996

[Traumatic total rupture of the musculus pectoralis major tendon].

Total or partial rupture of the major pectoral muscle is a rare lesion. Early treatment is recommended to regain full strength in the shoulder, but even without surgery 70 to 90% of original strength may be recovered within a year after trauma. We report a case in which a carpenter three months after total rupture of the major pectoral muscle tendon on the dominant side had spontaneously recovered sufficiently to perform his usual job. The diagnosis was visualized by MR imaging. The muscle strength was tested by use of a dynamometer.

Athletic Injuries↗
PubMed1996

Local recurrences in giant cell tumour of bone. Long-term follow up of 31 cases.

We studied the value of histopathological grading in determining the prognosis of giant cell tumour (osteoclastoma) and the rate of local and distant recurrences in a consecutive series of 31 patients. We found that grading had no prognostic value. Eighteen patients were treated by intralesional curettage and 13 by wide excision. Ten patients (56%), who were all treated by curettage, had local recurrences, but none of the tumours with wide excision recurred (p < 0.05). Five (16%) had local recurrences as well as distant metastases, usually to the lungs. The recurrences developed later than an average of 12 years after primary treatment in 3 patients. Wide excision and life-long follow up should be considered in the management of these tumours.

Adolescent↗
PubMed1996

A placebo- and active-controlled randomized trial of prophylactic treatment of seasonal allergic rhinitis with mometasone furoate aqueous nasal spray.

BACKGROUND: Topical nasal corticosteroids have become a mainstay of treatment for the symptoms of seasonal allergic rhinitis (SAR). It is likely that topical corticosteroids, by blocking an initial influx of inflammatory cells in the nasal mucosa induced by aeroallergens, may have a preventive effect on nasal allergy symptoms when administered before the pollen season. OBJECTIVE: This study was designed to assess the efficacy and safety of an 8-week course of mometasone furoate nasal spray (MFNS), 200 micrograms once daily, in the treatment of SAR compared with beclomethasone dipropionate aqueous nasal spray (BDP), 168 micrograms twice daily, and placebo vehicle, when treatment is initiated before the anticipated onset of the ragweed season. METHODS: Three hundred forty-nine patients with SAR to ragweed pollen from nine centers in the Northeast and Midwest of the United States were randomized to one of the three intranasal study medications (MFNS, 200 micrograms once daily, BDP, 168 micrograms twice daily, or placebo vehicle), starting 4 weeks before the estimated start of the ragweed season. RESULTS: The proportion of "minimal symptom" days (total nasal symptom score < or = 2) was statistically significantly higher in both the MFNS and BDP groups when compared with the placebo vehicle group (p < 0.01). The two active treatment groups were not statistically significantly different from each other. MFNS and BDP displayed a similar safety profile that did not differ from placebo. CONCLUSIONS: This suggests that MFNS, 200 micrograms (once daily), is a useful therapy in the prophylactic treatment of SAR.

Administration, Intranasal↗
PubMed1996

The effect of age on the apparent clearance of felbamate: a retrospective analysis using nonlinear mixed-effects modeling.

The effects of age on felbamate apparent clearance were examined through a retrospective analysis of plasma concentration data from 700 pediatric and adult epileptic patients (age range, 2-74 years) enrolled in six clinical studies. Patients received felbamate as monotherapy or in combination with either the antiepileptic drugs (AEDs) carbamazepine (CBZ), phenytoin (PHT), or valproate (VPA). Data were analyzed using a nonlinear mixed-effects pharmacostatistical modeling technique (NONMEM). Factors in the model included age, body weight, and concomitant AEDs. Apparent clearance was highest in the very young and decreased during the early teenage years, with minimal changes observed beyond 13 years. Mean apparent clearance values were approximately 40% higher in children (2-12 years) compared with those in adults (13-65 years). This pattern and its magnitude were consistent whether felbamate was administered alone or coadministered with CBZ, PHT, or VPA. The increase in clearance is minimal compared with other AEDs including PHT, CBZ, and phenobarbital. Enzyme-inducing AEDs (CBZ and PHT) increased felbamate apparent clearance by 32-38% relative to monotherapy, whereas coadministration with VPA had a minimal effect on felbamate apparent clearance. Dose/concentration linearity was observed at all ages during mono- or polytherapy. These findings suggest that felbamate dosing should be relatively uncomplicated in children relative to that in adults.

Adolescent↗
PubMed1996

Epithelial healing in the second eye after corneal abrasion.

Corneal epithelial healing velocity was determined in patients admitted to excimer laser photo refractive keratectomy, by daily video planimetry of the denuded area until complete healing. The epithelial healing process was followed in fellow eyes with regard to intervals between surgery of the two eyes of 1 to 10 weeks. In cases where the fellow eye was treated at one week after the first eye, the lesions healed significantly faster in the second eye as compared to patients with longer delay between the two operations.

Adult↗