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J Petersen

Publications and source records attributed to J Petersen.

At least 73 records · Page 4Linked to original sources

[An attempt to extract an intraretinal nematode located in the papillomacular bundle].

BACKGROUND: The nematode infection of the retina is a rare disease with sight threatening prognosis. Untreated eyes usually become blind. There are different types of clinical progression: granuloma causing tractional detachment chronic inflammation called diffuse unilateral subacute neuroretinitis (DUSN) and rapid loss of vision named "ocular wipe-out syndrome". Efficient drugs are not available. The progression of the disease can be stopped by killing the nematode by means of photocoagulation. For parasites in the periphery of the fundus this is the therapy of choice. Photocoagulation of the nematode close to the posterior pole can cause severe damage to the visual functions. There is a need for a less detrimental treatment. PATIENT AND METHODS: We report on a 48-year-old woman with an intraretinal nematode inside the papillomacular bundle. At an early stage of the disease with normal visual acuity the eye was vitrectomized and a posterior vitreous detachment performed. It was intended to extract the worm out of the retina in toto. The retina over the parasite was incised parallel to the nerve fibers, a tiny hook inserted and the worm pulled out. RESULTS: Only one half of the parasite could be removed since the adhesion of the parasite to the retina was stronger than its own cohesion. Nevertheless the inflammation rapidly regressed. Finally a small area of pigment mottling persisted around the former location of the parasite corresponding to a relative scotoma in the visual field. Visual acuity remained unchanged at full vision. CONCLUSION: We demonstrated that nematode larvae can be removed successfully from the central retina using vitrectomy techniques. By that means the damage to the visual functions can be limited. Near the posterior pole surgical extraction of the worm may be favorable compared to photocoagulation.

Animals↗

Mortality and causes of death of 513 Danish patients with systemic lupus erythematosus.

A multicentre cohort of 513 clinic attenders with systemic lupus erythematosus (SLE) was retrospectively identified, representing 4185 patient-years of follow-up. Expected numbers of death were calculated by means of age- and sex-specific mortality rates of the general Danish population. The observed number of deaths was 122. The survival rates were 97%, 91%, 76%, 64% and 53% after 1, 5, 10, 15, and 20 years respectively. The overall mortality rate was 2.9% per year (95% CI 2.4-3.5), and the standardized mortality rate (SMR) was 4.6 (95% CI 3.8-5.5). The causes of death included active SLE (n = 19), end stage organ failure due to SLE (n = 16), infections (n = 25), malignancy (n = 9), cardiovascular disease (n = 32), and other causes (n = 21). SLE was directly related to one third of the excess mortality. In conclusion, SLE patients in the present cohort had a 4.6-fold increased mortality compared with the general population and half of the deaths were caused by SLE manifestations or infections, especially in young patients during the early period of the disease.

Adolescent↗

Prognostic value of renal biopsy and clinical variables in patients with lupus nephritis and normal serum creatinine.

OBJECTIVE: To evaluate factors with possible influence on the renal outcome in patients with lupus nephritis but without chronic renal insufficiency (CRI). METHODS: Renal biopsies from 94 patients were re-assessed with regard to WHO class, activity, chronicity and tubulointerstitial indices without knowledge of clinical features. The outcome parameters were CRI defined as irreversibly increased serum creatinine and renal end stage disease. RESULTS: The risk ratios (RR) of developing CRI were 2.6 for active urinary sediment, 3.1 for hyaline thrombi and 7.3 for glomerular leukocyte exudation. The RR of renal end stage disease was 5.0 when the duration of renal disease exceeded one year at the time of biopsy and 4.3 when biopsy disclosed a class IV lesion. Glomerular sclerosis was also associated to renal end stage disease. CONCLUSION: Early renal biopsy and the abovementioned signs of active renal disease carry prognostic information that may have significant therapeutic implications.

Adolescent↗

Plo1 kinase recruitment to the spindle pole body and its role in cell division in Schizosaccharomyces pombe.

Polo kinases execute multiple roles during cell division. The fission yeast polo related kinase Plo1 is required to assemble the mitotic spindle, the prophase actin ring that predicts the site for cytokinesis and for septation after the completion of mitosis (Ohkura et al., 1995; Bahler et al., 1998). We show that Plo1 associates with the mitotic but not interphase spindle pole body (SPB). SPB association of Plo1 is the earliest fission yeast mitotic event recorded to date. SPB association is strong from mitotic commitment to early anaphase B, after which the Plo1 signal becomes very weak and finally disappears upon spindle breakdown. SPB association of Plo1 requires mitosis-promoting factor (MPF) activity, whereas its disassociation requires the activity of the anaphase-promoting complex. The stf1.1 mutation bypasses the usual requirement for the MPF activator Cdc25 (Hudson et al., 1990). Significantly, Plo1 associates inappropriately with the interphase SPB of stf1.1 cells. These data are consistent with the emerging theme from many systems that polo kinases participate in the regulation of MPF to determine the timing of commitment to mitosis and may indicate that pole association is a key aspect of Plo1 function. Plo1 does not associate with the SPB when septation is inappropriately driven by deregulation of the Spg1 pathway and remains SPB associated if septation occurs in the presence of a spindle. Thus, neither Plo1 recruitment to nor its departure from the SPB are required for septation; however, overexpression of plo1+ activates the Spg1 pathway and causes transient Cdc7 recruitment to the SPB and multiple rounds of septation.

Anaphase-Promoting Complex-Cyclosome↗

Validity of histopathological grading of articular cartilage from osteoarthritic knee joints.

OBJECTIVES: To determine the validity of the histological-histochemical grading system (HHGS) for osteoarthritic (OA) articular cartilage. METHODS: Human articular cartilage was obtained from macroscopically normal (n = 13) and OA (n = 21) knee joints. Sections of central and peripheral regions of normal samples were produced. Sections of regions containing severe, moderate, and mild OA changes were produced from each OA sample. A total of 89 sections were graded by means of the HHGS (0-14) twice by three observers. RESULTS: Average scores for regions designated severe (8.64) and moderate (5.83) OA were less than the expected (10-14 and 6-9, respectively) according to the HHGS, whereas average scores for the region designated mild (5.29) OA and central and peripheral regions (2.19) of normal cartilage were higher than expected (2-5 and 0-1, respectively). The HHGS was capable of differentiating between articular cartilage from macroscopically normal and OA joints and between the region designated severe OA and other regions. However, the HHGS did not adequately differentiate between regions designated mild and moderate OA. Values for sensitivity, specificity, and efficiency for all regions varied considerably. CONCLUSION: The HHGS is valid for normal and severe OA cartilage, but does not permit distinction between mild and moderate OA changes in articular cartilage.

Adolescent↗

Production of IL-1beta, IL-1 receptor antagonist and IL-10 by mononuclear cells from patients with SLE.

Depositions of immune-complexes are responsible for many of the pathological features of systemic lupus erythematosus (SLE). For example, immune-complex-induced tissue damage in glomerulonephritis has been shown to be mediated, at least in part, by interleukin (IL)-1. Inappropriate production or function of IL-1 may therefore contribute to disease manifestations in SLE. We investigated lipopolysaccharide (LPS)- and adherent IgG-stimulated release of IL-1beta, IL-1 receptor antagonist (IL-1ra) and IL-10, a potent modulator of IL-1, by blood mononuclear cells from patients with SLE. Mediator production was measured as ng cytokines/10(6) monocytes and compared with clinical parameters. Release of IL-1beta was only detectable in LPS-stimulated cultures and substantially reduced in patients with both active and inactive disease (P < 0.001). LPS-stimulated IL-1ra release was normal and the IL-1ra/IL-1beta ratio was therefore increased (P < 0.05) and correlated inversely to prednisolone dosage (P = 0.009). IgG-stimulated release of IL-1ra was reduced in patients with active disease compared to those with inactive disease and controls (P = 0.002). IL-10 release was similar in patients and controls. We conclude that monocytes from patients with active SLE are deficient in Fc gamma-R-mediated production of IL-1ra, whereas LPS-stimulated IL-1beta release by SLE monocytes is reduced regardless of disease activity. The former may contribute to immune-complex-mediated tissue damage in SLE.

Adult↗

Blunt chest trauma.

Blunt chest trauma represents a challenge to both nurses and physicians due to the frequent absence of clinical signs. When evaluating or predicting blunt chest trauma several components are important to remember.

Algorithms↗

Conjugation in S. pombe: identification of a microtubule-organising centre, a requirement for microtubules and a role for Mad2.

During the G1 phase of the cell cycle, cells of the fission yeast Schizosaccharomyces pombe can be induced to mate by nitrogen starvation and the presence of mating pheromones. Polarised growth towards cells of the opposite mating type (P or M) leads to the formation of a projection tip and, upon contact, localised cell wall degradation results in conjugation and cell fusion [1]. Here, we have investigated the role of microtubules in this process. We describe a previously unidentified microtubule-organising centre (MTOC) that forms at projection tips upon cell-to-cell contact, before cells fuse. Treatment of mating cells with the microtubule-destabilising drug thiabendazole (TBZ) showed that microtubule integrity was required for mating at two distinct stages: during projection tip formation and cell fusion. Projection tip formation requires filamentous (F) actin function [2] and microtubules are required for the localisation of F actin to the projection tip. We also identify a role during mating for Mad2--a mitotic checkpoint protein that is required in all eukaryotes to maintain the mitotic state in response to microtubule depolymerisation [3]. S. pombe mad2 mutant cells were compromised in their ability to mate upon removal of TBZ, indicating that in fission yeast, in the absence of microtubules, Mad2 is also required to maintain mating competence.

Actins↗

FH3, a domain found in formins, targets the fission yeast formin Fus1 to the projection tip during conjugation.

Formins are involved in diverse aspects of morphogenesis, and share two regions of homology: FH1 and FH2. We describe a new formin homology region, FH3. FH3 is an amino-terminal domain that differs from the Rho binding site identified in Bni1p and p140mDia. The Schizosaccharomyces pombe formin Fus1 is required for conjugation, and is localized to the projection tip in cells of mating pairs. We replaced genomic fus1+ with green fluorescent protein (GFP)- tagged versions that lacked either the FH1, FH2, or FH3 domain. Deletion of any FH domain essentially abolished mating. FH3, but neither FH1 nor FH2, was required for Fus1 localization. An FH3 domain-GFP fusion protein localized to the projection tips of mating pairs. Thus, the FH3 domain alone can direct protein localization. The FH3 domains of both Fus1 and the S. pombe cytokinesis formin Cdc12 were able to localize GFP to the spindle pole body in half of the late G2 cells in a vegetatively growing population. Expression of both FH3-GFP fusions also affected cytokinesis. Overexpression of the spindle pole body component Sad1 altered the distribution of both Sad1 and the FH3-GFP domain. Together these data suggest that proteins at multiple sites can interact with FH3 domains.

Actins↗

Liver repopulation with xenogenic hepatocytes in B and T cell-deficient mice leads to chronic hepadnavirus infection and clonal growth of hepatocellular carcinoma.

To investigate host and viral mechanisms determining hepadnaviral persistence and hepatocarcinogenesis, we developed a mouse model by transplanting woodchuck hepatocytes into the liver of mice that contain the urokinase-type plasminogen activator transgene (uPA) and lack mature B and T lymphocytes due to a recombination activation gene 2 (RAG-2) gene knockout. The woodchuck hepatocytes were transplanted via intrasplenic injection and were found to integrate into the recipient mouse liver cord structure. Normal adult woodchuck hepatocytes proliferated and reconstituted up to 90% of the uPA/RAG-2 mouse liver. uPA/RAG-2 mice containing woodchuck hepatocytes were infectable with woodchuck hepatitis virus (WHV) and showed WHV replication for at least 10 months with titers up to 1 x 10(11) virions per ml in the peripheral blood. WHV-infected hepatocytes from chronic carrier woodchucks also established a persistent infection in uPA/RAG-2 mice after an 8- to 12-week lag period of viremia. Although WHV envelope, core, and X proteins were produced in the uPA/RAG-2 mice, no inflammatory host immune response was observed in the liver of WHV-replicating mice. A first antiviral test demonstrated a greater than four orders of magnitude drop in WHV titer in response to interferon alpha treatment. WHV replication was up-regulated by dexamethasone treatment. Comparison of precancerous lesions in donor woodchucks versus recipient uPA/RAG-2 mice revealed an enrichment of dysplastic precancerous hepatocytes in transplanted mice. Clonal amplification of hepatocytes from a woodchuck with hepatocellular carcinomas was demonstrated by the detection of unique WHV DNA integration patterns in hepatocellular carcinomas that arose in uPA/RAG-2 mice. In the absence of B or T cell-mediated immune responses, WHV establishes a persistent noncytotoxic infection of woodchuck hepatocytes in uPA/RAG-2 chimeric mouse livers. Further studies of the kinetics of hepadnavirus infection and replication in quiescent and proliferating hepatocytes should increase our understanding of hepadnavirus spread and aid in the design of therapies to block or cure persistent infection.

Animals↗

A multicentre study of 513 Danish patients with systemic lupus erythematosus. I. Disease manifestations and analyses of clinical subsets.

A Danish multicentre study was undertaken of the manifestations, infections, thrombotic events, survival and predictive factors of survival in 513 Danish patients with systemic lupus erythematosus (SLE) according to the 1982 classification criteria of the American College of Rheumatology. The mean duration of follow-up was 8.2 years from diagnosis and 12.8 years from first symptom. This paper describes the most common clinical and laboratory manifestations and their relationship to sex and age at the time of onset and diagnosis. Cluster analysis revealed three clinically defined clusters at the time of disease onset. Cluster 1 (57% of patients) consisted of relatively elderly patients without nephropathy or malar rash, but with a high prevalence of discoid lesions. Cluster 2 (18%) consisted of patients with nephropathy, a third of whom also developed serositis and lymphopenia. The patients of the third cluster (25%) all had malar rash and half were photosensitive. Follow-up showed that the patients of cluster 2 developed azotaemia, large proteinuria, arterial hypertension and myositis significantly more often than did the rest of the patients, but the mortality was not increased. The risk of developing renal end-stage disease was highest in men with early-onset disease.

Adolescent↗

A multicentre study of 513 Danish patients with systemic lupus erythematosus. II. Disease mortality and clinical factors of prognostic value.

In this Danish multicentre study, predictive clinical factors of mortality and survival were calculated for 513 patients with systemic lupus erythematosus (SLE), 122 of whom died within a mean observation period of 8.2 years equalling a mortality rate of 2.9% per year. Survival rates were 97%, 91%, 76% and 64% after 1, 5, 10 and 15 years, respectively. The direct causes of death included SLE (n = 35), infections (n = 25), malignancy (n = 9), cardiovascular disease (n = 32) and other causes (n = 21). Uni- and multivariate analyses of survival and mortality were performed for all deaths and for SLE-related deaths. Azotaemia (one-fifth of the patients) was a strong predictor of increased overall and SLE-related mortality, but nephropathy per se (one-half of the patients) and large proteinuria (one-sixth of the patients) were unrelated to survival. Haemolytic anaemia had a significant negative influence on survival related to mortality caused by infections. Diffuse central nervous system disease and myocarditis were related to increased SLE-related mortality, whereas photosensitivity predicted a decreased mortality. Non-fatal infections and thrombotic events predicted a decreased overall survival. Since 1980 the mortality caused by SLE manifestations has decreased significantly.

Adolescent↗

Visual fields after removal of subretinal hemorrhages and neovascular membranes in age-related macular degeneration.

BACKGROUND: Surgical removal of subretinal hemorrhaging and membranes in eyes with age-related macular degeneration is feasible from a technical point of view, but no advantage over the spontaneous course of the disease has been proven. Visual acuity usually does not improve much. A realistic aim of surgical intervention may be diminution of the central scotoma size, which has not been studied. METHOD: In a prospective study visual fields were measured preoperatively and 6 weeks and 6 months postoperatively in eyes operated on for subretinal hemorrhages and membranes in exudative age-related macular degeneration. The OCTOPUS 1-2-3 program glx, which tests the visual field of 60 degrees diameter at 59 points, was used. Changes in the total size of areas with sensitivity loss of 10-20 dB (= relative scotoma) and > 20 dB (= absolute scotoma) were interpreted as surgical effect. Patients with postoperative retinal detachment or neovascular recurrence were excluded. 30 eyes of 29 patients were enrolled (mean age 75.3 years, 11 male, 18 female) and divided into 3 groups: 14 eyes with massive subretinal hemorrhage of diameters > 30 degrees; 12 eyes with hemorrhages of 10 degrees-30 degrees; 4 eyes with mere neovascular membranes < 10 degrees. RESULTS: (1) The visible area of damage is diminished by surgery (P < 0.01). The reduction for lesions > 30 degrees is 80%; for lesions between 10 degrees and 30 degrees the improvement is 43%. For lesions < 10 degrees there is no significant change. (2) The absolute scotoma size diminishes in all three groups (P = 0.05). The reductions are 63%, 57% and 21%, respectively. (3) Areas of absolute scotoma do not regain full function but are converted to relative scotoma depth, at best. Therefore, in the > 30 degrees group an overall increase (P < 0.01) of the relative scotoma size is observed. (4) The mean sensitivity in the 60 degrees field enhances by 1.6 dB (average over 30 eyes, P = 0.04). (5) Mean preoperative visual acuities were 0.03, 0.12 and 0.17, respectively, with no significant change after surgery. The power of testing is sufficient (0.93) to reject an increase of acuity from 0.12 to 0.2 in group 2. CONCLUSIONS: For hemorrhagic subretinal lesions of diameter > 10 degrees a relevant reduction of central scotoma size is achieved by surgery. The final benefit for the patients depends on the frequency of surgical complications and neovascular recurrence.

Aged↗

Renal artery stenosis in kidney transplants.

Transplant renal artery stenosis (TRAS) is an increasingly recognized complication of renal transplantation, with a reported incidence of between 1% and 23%. The clinical features include refractory hypertension, new-onset hypertension, allograft dysfunction, and the presence of a bruit over the graft. In this report, we describe the investigation and treatment of one such patient and review the current diagnostic approaches and therapy in this setting.

Adult↗

Clinical features and serum antinuclear antibodies in 230 Danish patients with systemic sclerosis.

The objective was to investigate the relationship between the presence of different types of antinuclear antibodies (ANA) in patients with systemic sclerosis (SSc) and the presence of clinical features. Sera from 230 patients with SSc were tested for the presence of ANA, including anticentromere antibodies (ab), antitopoisomerase I ab, anti-U1 RNP ab and antinucleolar ab, including anti-Th RNP, anti-U3 RNP and anti-U17 RNP. Clinical features were registered prospectively in a clinical database. Eighty-two per cent of the patients were women. The median age was 58 yr (45-67, quartiles) and median age at disease onset was 44 (30-55) yr. ANA were found in 86% of the patients (anticentromere: 34%; antitopoisomerase I: 14%; anti-U1 RNP: 6.5%; antinucleolar total: 16%; anti-Th RNP: 2.2%; anti-U3 RNP: 3.5%; anti-U17 RNP: 0%). Anticentromere ab were found to be related to a high prevalence of calcinosis, telangiectasia, digital ulcers, acrosclerosis, primary biliary cirrhosis, isolated reduction of pulmonary diffusing capacity, and a low prevalence of radiological evidence of pulmonary fibrosis. Antitopoisomerase I ab were associated with a high prevalence of digital joint deformity, distal osteolysis, radiological signs of pulmonary fibrosis, a low prevalence of calcinosis and late onset of disease. Anti-U1 RNP ab were related to a high prevalence of arthritis and myositis, a low prevalence of calcinosis, and early disease onset. The presence of antinucleolar ab, including anti-U3 RNP and anti-Th RNP, was not significantly related to any particular clinical features in this study; possibly due to the small number of patients with these ab. The presence of anticentromere, antitopoisomerase I and anti-U1 RNP ab in the serum was also found to have previously described clinical correlations in a group of Danish SSc patients.

Adolescent↗

Metabolic labeling of woodchuck hepatitis B virus X protein in naturally infected hepatocytes reveals a bimodal half-life and association with the nuclear framework.

In order to identify potential sites of hepadnavirus X protein action, we have investigated the subcellular distribution and the stability of woodchuck hepatitis virus (WHV) X protein (WHx) in primary hepatocytes isolated from woodchucks with persistent WHV infection. In vivo cell labeling and cell fractionation studies showed that the majority of WHx is a soluble cytoplasmic protein while a minor part of newly synthesized WHx is associated with a nuclear framework fraction (20%) and with cytoskeletal components (5 to 10%). Pulse-chase experiments revealed that cytoplasmic WHx has a short half-life and decays with bimodal kinetics (approximately 20 min and 3 h). The rates of association and turnover of nucleus-associated WHx suggest that compartmentalization may be responsible for the bimodal turnover observed in the cytoplasm.

Animals↗

Expression of alpha and beta subunits of the integrin superfamily in articular cartilage from macroscopically normal and osteoarthritic human femoral heads.

OBJECTIVE: The objective of this study was to detail the topographical and zonal distribution of alpha and beta subunits of the integrin superfamily in normal and osteoarthritic cartilage. METHODS: Immunohistochemistry utilising antibodies towards alpha and beta subunits was performed on cryostat sections of human articular cartilage from macroscopically normal (n = 6) and osteoarthritic (n = 6) femoral heads. Samples of articular cartilage were obtained from 12 topographically distinct sites from each femoral head. Each section was divided into zones (superficial, middle, deep) and staining scores were recorded. RESULTS: Normal cartilage stained for integrin subunits alpha 1, alpha 5, alpha V, beta 1, beta 4, and beta 5, but not for alpha 2, alpha 3, alpha 4, alpha 6, beta 2, beta 3, and beta 6. Intact and non-intact residual cartilage from osteoarthritic femoral heads stained for alpha 1, alpha 2, alpha 5, alpha V, beta 1, beta 4, and beta 5. Staining was occasionally seen for alpha 4 and beta 2, but not for alpha 3, alpha 6, beta 3, and beta 6. There was no topographical variation in the staining for any of the subunits in either normal or osteoarthritic cartilage. The only subunit that displayed a zonal variation was alpha V; staining for this subunit was most pronounced in the superficial zone compared with the middle and deep zones. CONCLUSION: Chondrocytes in normal and osteoarthritic cartilage express the integrin subunits alpha 1, alpha 5, alpha V, beta 1, beta 4, and beta 5. Chondrocytes in osteoarthritic cartilage, in addition, express the alpha 2, alpha 4, and beta 2 subunits. The alpha v subunit is expressed by more chondrocytes in the superficial zone in comparison with cells in the deeper zones. None of the subunits display topographical variation in expression.

Aged↗