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Biomedical subjects

J Winther

Publications and source records attributed to J Winther.

At least 19 recordsLinked to original sources
PubMed2000

Purification, co-crystallization and preliminary X--ray analysis of the natural aspartic proteinase inhibitor IA3 complexed with saccharopepsin from Saccharomyces cerevisiae.

The vacuolar aspartic proteinase from baker's yeast, saccharopepsin, has been co-crystallized with its natural inhibitor I(A)3, found in the cytosol. The I(A)3-saccharopepsin complex crystals belong to the space group P6(2)22, with unit-cell parameters a = b = 192.1, c = 59. 80 A and one molecule per asymmetric unit. The initial X-ray analysis of the complex indicates that the crystals diffract to 5.0 A, similar to native saccharopepsin crystals. This is probably a consequence in part of glycosylation of the native saccharopepsin. Full structural analysis of the complex crystal is in progress.

Aspartic Acid Endopeptidases↗
PubMed1999

Relationship between brain structure sizes and performing rapid limb movements. A quantitative magnetic resonance study.

In this study, we aimed to determine the relationship between the size of cerebral structures evaluated by quantitative magnetic resonance technique and the ability of performing rapid-velocity limb movements. Forty-seven healthy women with a mean age of 43.4 years (range 22-68) were included. Exclusion criteria were systemic diseases including alcoholism. Finger and ankle tapping were quantitatively recorded for both right and left extremities. A mean value for the right and left side was calculated. To determine atrophy, we measured the area of the corpus callosum, the cerebrum and the cerebellum on midline sagittal sections. On transverse images, the ventricle-to-brain ratio, the bifrontal ratio and the bicaudate ratio were selected as atrophy parameters. Also, the prevalence of white matter hyperintensities was assessed. Fifteen (32%) had hyperintense white matter lesions. Using simple regression analysis, the frequencies of both finger (r = 0.37, beta = -0.002, p = 0.022) and ankle (r = 0.35, beta = -0.001, p = 0.032) tapping were associated with reduced cerebellar size. No association was found for other atrophy parameters or the number of hyperintense white matter lesions. This study indicates that impaired ability to perform fast limb movements may be related to a relative cerebellar atrophy.

Adult↗
PubMed1995

The anastomosis angle does change the flow fields at vascular end-to-side anastomoses in vivo.

PURPOSE: The purpose of this article was to study the influence of the anastomosis angle on the flow fields at end-to-side anastomoses in vivo. METHODS: Polyurethane grafts of similar internal diameter to that of the abdominal aorta (8 mm) were implanted from the suprarenal to the infrarenal level in 10 pigs. Three angles of standardized distal end-to-side anastomoses (90 degrees, 45 degrees, and 15 degrees) were studied. The anatomic position of the anastomoses was constant, the proximal outflow segment was occluded, and the flow rate through the graft was controlled. Flow visualization was accomplished by a color-flow Doppler ultrasound system. RESULTS: The angulation was reproduced within 10%. Gross hemodynamic parameters were stable, and the similarity parameters were typical for peripheral bypasses (mean Reynold's number is 424 and Womersley's parameter is 5.9). The flow fields were clearly dependent on the anastomosis angle. A zone of recirculation (approximately 5% of the flow area), extending from the toe to one diameter downstream, was found in the 45-degree and 90-degree anastomoses. No flow disturbances were detected at the toe and one diameter downstream with an anastomosis angle of 15 degrees. At the heel different recirculating flow patterns were found in the different anastomoses. CONCLUSION: The anastomosis angle does change the flow fields at vascular end-to-side anastomoses in vivo.

Anastomosis, Surgical↗
PubMed1995

An in vivo model for studying the local haemodynamics of end-to-side anastomoses.

OBJECTIVES: To develop an in-vivo model to study the anastomotic flow patterns. DESIGN: Prospective, open, animal study. METHODS: Polyurethane grafts with an internal diameter equal to the abdominal aorta (8 mm) of 90 kg pigs were implanted as bypass grafts from the supra-renal to the infra-renal level. A novel technique for constructing anastomoses with different anastomosis angles and only slight dilatation was used. The proximal outflow segment was occluded and the flow rate through the graft controlled by clamping the iliac arteries. Visualisation of the flow-fields at the distal end-to-side anastomosis was achieved by a comprehensive colour Doppler mapping protocol. RESULTS: The angulation of the anastomoses was controllable and reproducible. Gross haemodynamic parameters were stable within physiological ranges and were typical for peripheral bypass grafts. The flow fields at the distal end-to-side anastomosis were visualised and found to be in accordance with those reported by in vitro studies. Using different angles of Doppler insonation the same flow field characteristics were found. CONCLUSIONS: The model is an appropriate tool for studies of the effects of anastomotic geometry on local flow fields in vivo.

Anastomosis, Surgical↗
PubMed1993

Velocity profiles in the ascending aorta in pigs: axial development and influence of changes in left ventricular contraction pattern.

Earlier studies using hot-film anemometry in pigs have revealed skewed tangentially rotating velocity profiles in the ascending aorta during systole. The reason for this phenomenon has been postulated to be caused by the left ventricular contraction pattern. Therefore, the aim of this study was to investigate the influence of the left ventricular contraction pattern on the velocity fields in the ascending aorta of pigs. We used a 10 MHz perivascular pulsed Doppler ultrasound system to measure point blood velocities at two axial locations over the entire cross sectional area in the ascending aorta of 90 kg pigs. The axial component of the velocity profiles was visualized dynamically by computerized 3-dimensional animation techniques. Changing left ventricular contraction patterns were accomplished by reversible occlusion of either the left anterior descending or right posterior descending coronary artery. The axial development of the systolic rotating and skewed velocity profiles in the ascending aorta was described. The appearance of the systolic velocity profiles were virtually unaffected by changes in left ventricular contraction pattern.

Animals↗
PubMed1990

Risk of nonocular cancer in first-degree relatives of retinoblastoma patients.

The increased risk of nonocular cancer seen consistently in studies of survivors of retinoblastoma may be caused in part by the presence of a retinoblastoma gene that also predisposes to other cancers. It has been claimed that this gene also increases the risk for cancer among unaffected relatives of genetic retinoblastoma probands. We report here a population-based study of the risk of nonocular cancer in parents and siblings of persons notified to the Danish Cancer Registry with retinoblastoma during 1943-84. No excess was observed among first degree relatives of 61 genetic retinoblastoma probands, whereas a slight (10%) excess was seen among the parents of 115 nongenetic probands. The latter was the result of significant excesses of malignant melanoma (4 observed, 0.4 expected), multiple myeloma (2 observed, 0.2 expected) and osteogenic sarcoma (1 observed, 0.03 expected). The observed risk pattern cannot be explained by the presence of the retinoblastoma gene.

Adult↗
PubMed1989

Effect of photofrin II and light energy on retinoblastoma-like cells in vitro. Dose-response relationships, effect of light dose rate and recovery ratio.

A clonogenic survival assay on retinoblastoma-like cells (EXP-5 cells) was applied in vitro to assess the effect of photodynamic therapy at relative low concentrations of photofrin II and high doses of light energy. The cellular concentration of photofrin II was estimated by spectrofluorimetry. The cellular content of photofrin II increased with the concentration in the medium (up to 3 micrograms/ml) and the incubation time (up to 24 h) in cells first incubated in photofrin II for 24 h and then in photofrin-II-free medium for 24 h. There was an obvious dose-response relationship between cell damage and photodynamic therapy both for the cellular photofrin II content and the total amount of light energy delivered. The dose rate of light energy had no influence on the cell damage. The cells had a recovery factor of only 1.34, suggesting a low repair of sublethal damage. An approximately linear isoeffect curve at the 10% survival level was described as a function of photofrin II concentration and light energy, suggesting a predictable reversible relationship between them. The results suggest that retinoblastoma cells are very sensitive to photodynamic therapy.

Animals↗
PubMed1989

Photodynamic therapy effect in an intraocular retinoblastoma-like tumour assessed by an in vivo to in vitro colony forming assay.

Cell survival was investigated in an intraocular retinoblastoma-like tumour 30 min to 48 h after photodynamic therapy. The survival of the cells was assessed by an in vivo to in vitro colony forming assay, estimated by either the plating efficiency of the treated tumour cells compared to non-treated cells or the number of clonogenic cells per mg excised tumour. Curves showing cell survival as a function of the time between light irradiation and excision of the intraocular tumours were biphasic. This suggests more than one PDT tissue destruction mechanism in vivo (i.e. an early direct cell damage plus a subsequent late damage occurring in the tumour tissue left in situ after treatment). The delayed mechanism may be due to changes in the environment of the tumours probably caused by vascular damage. Tumour cells sensitised by Photofrin II in vivo and excised from the eyes were damaged by light when irradiated in vitro and this was dependent on the light energy dose. This showed that cellular Photofrin II uptake in the eye tumours was sufficient for direct cell damage and thus supports the suggestion that direct and indirect tumour destruction occurs in this eye tumour after photodynamic therapy.

Animals↗
PubMed1989

Photodynamic therapy of experimental intraocular retinoblastomas--dose-response relationships to light energy and photofrin II.

The destructive effect on tumour tissue and on normal eye tissue of photodynamic therapy has been investigated in rat eyes containing fast growing retinoblastoma-like tumours. Tumour response was described in terms of local control 90 days after treatment. The curability increased up to a maximum when large Photofrin II doses or light energy doses were administered. Early damage of conjunctiva or cornea also increased with large treatment doses and was an important limitation factor for improvement of the curability in the current model. The level of normal tissue damage decreased rapidly with increasing intervals between administration of Photofrin II and light, suggesting that conjunctival or corneal damage may not be a limitation factor 3-5 days after Photofrin II administration. A reciprocal relationship between light energy doses and Photofrin II doses was demonstrated both for curability and for the normal tissue damage. The results suggested that 2.5 mg/kg Photofrin II in combination with an extended light irradiation provoked less normal tissue damage than 10 mg/kg Photofrin II in combination with an equivalent shorter light exposure in order to obtain 15% curability of the animals.

Animals↗
PubMed1989

Vascular effects of photodynamic therapy in an intraocular retinoblastoma-like tumour.

Results from experimental tumours suggest that the mechanism of action of photodynamic therapy (PDT) involves both a direct killing of tumour cells, and a secondary effect resulting from vascular damage. We have investigated the possible vascular changes induced by PDT in an intraocular retinoblastoma-like rat tumour model using the 86RbCl extraction procedure. Light irradiation (90 J/cm2; 633 nm; 30 min) of intraocular tumours 24 h after an intraperitoneal injection of 5 mg/kg Photofrin II produced an increase in the tumour uptake of 86RbCl during the treatment period. However, 24 h later these values had decreased to 25% of that normally found in control animals. These effects were observed in both the tumour material and associated normal eye tissue, but not in PDT treated normal eyes without tumours. The results confirm that the vasculature of this eye tumour model is a target for some of the PDT effects.

Animals↗
PubMed1988

Risk of nonocular cancer among retinoblastoma patients and their parents. A population-based study in Denmark, 1943-1984.

The risk of nonocular cancer among survivors of retinoblastoma has been investigated in a population-based study in Denmark, 1943 to 1984. None of the survivors had been treated with chemotherapeutic drugs. Forty-eight patients were treated with x-rays, and 102 patients were treated primarily with surgical removal of the eye(s). The overall relative risk (RR) for a new primary cancer was 4.2 (95% confidence limits, 1.1-11.5). In the subgroup of genetic retinoblastoma the risk was 15.4 (95% confidence limits, 2.6-50.8) and in the group of nonhereditary cancer the risk was 1.7 (95% confidence limits, 0.1-8.5). For all retinoblastoma patients the RR of bone cancer was 100 (95% confidence limits, 17-330). Parents not having retinoblastoma themselves were not at increased risk for nonocular cancer.

Adolescent↗
PubMed1988

Predictive value of flow cytometric DNA-analysis on fresh retinoblastoma tissue.

The cellular DNA content and the distribution of tumour cells in different phases of the cell cycles has been analysed in 8 consecutive enucleated eyes with retinoblastoma. All tumours had abnormal ploidy levels. The analysis did not reveal any specific pattern in 2 tumours which had metastasized compared to 6 local tumours. The flow cytometric analysis alone or in combination with histopathology appeared not to improve the classification of large retinoblastomas.

Child, Preschool↗
PubMed1988

Histopathological changes in an intraocular retinoblastoma-like tumour following photodynamic therapy.

The histopathological effect of photodynamic therapy (PDT) was investigated in an intraocular retinoblastoma-like tumour in vivo. Eighty-two tumours were studied by light microscopy and 8 by electron microscopy. Damage of the vascular endothelium with dilation of the organelles was evident 1 h after treatment, followed by leakage of the blood vessels, tissue hemorrhages, and vascular collapse. Histopathological examination showed an overall pattern of shrinkage of the cytoplasm and pycnosis of the nuclei in most of the tumour cells 3-5 days after treatment. The tumour recurrence often developed from the periphery of the tumours and in a few cases from small islets of viable tissue. Use of high doses of Photofrin II or light energy was associated with damage in the light irradiated area both to the conjunctiva or cornea in the form of leucocyte infiltration or ulcers, and to the retina, which often developed edema and appeared severely disorganized, with damage of the photoreceptors.

Animals↗
PubMed1988

Amplification of the human putative oncogene INT1 in primary retinoblastoma tumors.

We report the amplification of the putative oncogene INT1 in two of four retinoblastomas. In one case, the INT1 signal was amplified 10 to 15-fold, in the other 100-fold. In both cases there were signs of increased tumor aggressiveness with invasion of the choroid and development of metastases. The two cases without INT1 amplification had neither metastases nor locally invasive growth. Our findings indicate that INT1 amplification may be a feature of increased malignant potential in retinoblastomas.

Blotting, Southern↗
PubMed1987

Experimental studies of photodynamic therapy in a retinoblastoma-like tumour.

Combination therapy with a purified hematoporphyrin derivative, Photofrin II, and red light (photodynamic therapy) was investigated in a retinoblastoma-like tumour growing in the eyes of rats in vivo and in cell cultures. There was a marked dose-response relationship between Photofrin II and the light energy both in vitro and in vivo. Up to 33% of the tumours could be controlled in vivo. In vivo/in vitro assays indicated Photofrin II uptake in the tumour cells in vivo in relation to the administered doses. Studies of cell death kinetics suggested that the mechanisms of photodynamic therapy were both a primary cell kill effect and a secondary tissue destruction, probably as a consequence of vascular damage.

Animals↗
PubMed1987

Non-ocular cancer in retinoblastoma survivors.

The risk of non-ocular cancer has been investigated in 150 surviving Danish patients with retinoblastoma diagnosed in the period 1943-1984. None of the patients had been treated with chemotherapeutic drugs. The overall relative risk of non-ocular cancer was 4.2 (95% confidence limits, 1.1-11.5). In the subgroups of hereditary retinoblastoma, the relative risk was 15.4 (95% confidence limits, 2.6-50.8), and in the subgroups of non-hereditary retinoblastoma the relative risk was 1.7 (95% confidence limits (0.1-8.5). The risk of cancer among 267 parents of retinoblastoma children was not different from that of the general population.

Eye Neoplasms↗