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Biomedical subjects

M O Jensen

Publications and source records attributed to M O Jensen.

10 recordsLinked to original sources
PubMed2001

The mechanism of glycerol conduction in aquaglyceroporins.

BACKGROUND: The E. coli glycerol facilitator, GlpF, selectively conducts glycerol and water, excluding ions and charged solutes. The detailed mechanism of the glycerol conduction and its relationship to the characteristic secondary structure of aquaporins and to the NPA motifs in the center of the channel are unknown. RESULTS: Molecular dynamics simulations of GlpF reveal spontaneous glycerol and water conduction driven, on a nanosecond timescale, by thermal fluctuations. The bidirectional conduction, guided and facilitated by the secondary structure, is characterized by breakage and formation of hydrogen bonds for which water and glycerol compete. The conduction involves only very minor changes in the protein structure, and cooperativity between the GlpF monomers is not evident. The two conserved NPA motifs are strictly linked together by several stable hydrogen bonds and their asparagine side chains form hydrogen bonds with the substrates passing the channel in single file. CONCLUSIONS: A complete conduction of glycerol through the GlpF was deduced from molecular dynamics simulations, and key residues facilitating the conduction were identified. The nonhelical parts of the two half-membrane-spanning segments expose carbonyl groups towards the channel interior, establishing a curve-linear pathway. The conformational stability of the NPA motifs is important in the conduction and critical for selectivity. Water and glycerol compete in a random manner for hydrogen bonding sites in the protein, and their translocations in single file are correlated. The suggested conduction mechanism should apply to the whole family.

Amino Acid Motifs↗
PubMed2001

Dynamics of the substrate binding pocket in the presence of an inhibitor covalently attached to a fungal lipase.

To gain insight into the mobility of the occupied ligand-binding pocket of the Rhizomucor miehei lipase we have conducted a rigorous molecular dynamics analysis. The covalently attached inhibitor, ethylhexylphosphonate, was employed as a mimic of the putative tetrahedral intermediate in the esterolytic reaction. Our results show that in this lipase, ligand recognition is influenced by the flexibility of the binding pocket, a feature that is common to many other enzymes. Several regions around the active site were found to move significantly to adapt to the inhibitor. These motions are correlated to the flexibility of the inhibitor. In particular, the hexyl chain of the inhibitor shows considerable mobility, and adjacent residues in the binding cleft accommodate to this flexibility. Pronounced fluctuations in the binding pocket induced by the flexibility of the inhibitor are observed in the hinge region F79-S82, the active site loop region W88-V95 and the protein regions P209-F215/H257-Y260. The flexibility in the regions F79-S82 and H257-Y260, where the shorter ethyl chain is located, indicates that additional space in this binding cleft region is available for accommodating a larger moiety. Fluctuations in the region W88-V95 and P209-F215 are due to the relatively short flexible hexyl carbon chain. This part of the binding pocket could be stiffened by the presence of a longer carbon chain. Though the inhibitor is covalently attached through the phosphonate moiety, interaction of the remainder of the molecule and the enzyme are determined by hydrophobic interactions, where the Van der Waals energies are approximately 25% lower than the electrostatic contributions.

Catalytic Domain↗
PubMed2001

Improved in vitro quantification of the force exerted by the papillary muscle on the left ventricular wall: three-dimensional force vector measurement system.

Recent developments indicate that the forces acting on the papillary muscles can be a measure of the severity of mitral valve regurgitation. Pathological conditions, such as ischemic heart disease, cause changes in the geometry of the left ventricle and the mitral valve annulus, often resulting in displacement of the papillary muscles relative to the annulus. This can lead to increased tension in the chordae tendineae. This increased tension is transferred to the leaflets, and can disturb the coaptation pattern of the mitral valve. The force balance on the individual components governs the function of the mitral valve. The ability to measure changes in the force distribution from normal to pathological conditions may give insight into the mechanisms of mitral valve insufficiency. A unique in vitro model has been developed that allows quantification of the papillary muscle spatial position and quantification of the three-dimensional force vector applied to the left ventricular wall by the papillary muscles. This system allows for the quantification of the global force exerted on the posterior left ventricular wall from the papillary muscles during simulation of normal and diseased conditions.

Animals↗
PubMed2001

Harvested porcine mitral xenograft fixation: impact on fluid dynamic performance.

BACKGROUND AND AIM OF THE STUDY: Recent developments suggest that stentless bioprosthetic mitral valve heterografts should be considered in order to optimize valve hydrodynamics. The fixation process alters the mechanical properties of tissue. This study investigates the changes in mitral valve morphology and hemodynamic performance following fixation. METHODS: Porcine mitral valves were excised and attached to a physiological annular ring. Mitral valve function was studied in vitro with a rigid transparent left heart model, allowing transverse and sagittal views. Initial experiments were performed with fresh valves under physiological conditions. Three different papillary muscle positions were used, and each was recorded. After glutaraldehyde fixation, genipin fixation, and cryopreservation, the valves were re-studied while maintaining cardiac output. Performance characteristics before and after fixation were obtained from hydrodynamic pressure and flow data, high-speed video camera, digital video, Doppler ultrasound, and three-dimensional papillary muscle force measurements. Morphology changes were detected by detailed anatomic measurements of the valves before and after fixation. RESULTS: Valve length was reduced by 18.5% after fixation with genipin (p <0.001), but not with glutaraldehyde. Cryopreserved valves showed no statistically significant changes in morphology or hydrodynamic performance after preservation. The forward flow opening area was reduced by 12.2% (p <0.001) after glutaraldehyde fixation, and by 32.3% (p = 0.004) after genipin fixation. Thus, maximal forward flow velocity was increased by 33.3% (p = 0.008) after glutaraldehyde fixation and by 52.8% (p = 0.001) after genipin fixation. The flow acceleration was consistent with a funnel shape of the fixed valves causing important flow contraction beyond the orifice (vena contracta). The papillary muscle force increased with apically posterior papillary muscle displacement by 20.4% (p = 0.001) and 101.5% (p <0.001) after glutaraldehyde and genipin fixation, respectively, and total regurgitant volume was increased by 91.6% (p <0.001) and 117.3% (p <0.001), respectively. The work required by the heart simulator to maintain a constant cardiac output at constant vascular resistance increased by 24.2% (p = 0.003) and 34.2% (p = 0.004) after glutaraldehyde and genipin fixation, respectively. CONCLUSION: The present study shows that chemical fixation of porcine mitral valves adversely affects the hemodynamics of the valves, increasing overall workload. The effects were more severe after fixation with genipin than with glutaraldehyde. This suggests the need to explore other fixation agents to optimize valvular cardiac function. Cryopreservation had no detrimental effects on valvular hemodynamic performance.

Animals↗
PubMed1999

Mitral valve compensation for annular dilatation: in vitro study into the mechanisms of functional mitral regurgitation with an adjustable annulus model.

BACKGROUND AND AIM OF THE STUDY: Mitral annulus dilatation has been identified as an important factor in functional mitral regurgitation (FMR). However, the pathophysiologic interaction of annular dilatation and papillary muscle (PM) displacement in FMR, which occurs clinically in left ventricular (LV) dilatation, is still not well understood. It is difficult to separate these competing factors in vivo, leading to confusion in identifying the real role of the annular dilatation in FMR and its interaction with PM displacement. METHODS: To better understand the competing factors, an in vitro model was developed with a D-shaped adjustable mitral annulus that could be changed from 5.5 cm2 to 13.0 cm2 during experiments, independent of varying PM positions. Six excised normal porcine mitral valves were mounted in a left ventricular model with the adjustable annulus device and tested in a physiologic pulsatile flow system under normal cardiac output and left ventricular pressure (5.0 l/min, 120 mmHg). Papillary muscles were placed in normal and then displaced to an apical posterolateral position, to simulate pathological conditions seen clinically. Regurgitation was measured directly by a flow probe and the mitral valve geometry and leaflet coaptation were recorded by video camera through the model's atrium window. In addition, 2D echocardiography was used to evaluate leaflet coaptation and color Doppler flow mapping to detect the regurgitant flow field. RESULTS: The results showed that in normal PM position, the mitral regurgitant was consistently at low level until the annulus was enlarged to 1.75 times the normal size, at which time it increased sharply. Papillary muscle apical posterolateral displacement, which simulates a dilated LV, caused regurgitation to occur earlier (1.5 times the normal annulus size), and had an increased regurgitant volume (p < 0.05). The leaflet gaps were first observed at the commissural areas of the valves, consistent with the location of regurgitant jets detected by color Doppler flow mapping. Asymmetric PM displacement created more regurgitation than both the symmetric PM tethering (p = 0.063) and normal PM position (p < 0.01). The regurgitant jets were observed at the same commissural side as the PM displacement, even without significant enlargement of the annulus. CONCLUSIONS: This in vitro study provides insight into the interaction between annular dilatation and PM displacement on FMR. The resulting effects and their overall similarity to clinical observation could help further understand the mechanism of FMR and provide additional information to improve future therapeutic strategies.

Dilatation, Pathologic↗
PubMed1992

Thyroid and thymic malignancy following childhood irradiation.

Synchronous thyroid and thymic malignancy following childhood thymic irradiation has only been reported in two known cases previously, with a third case identified here. A rationale is presented for following these radiated patients as they age with thyroglobulin and thyroid-stimulating hormone (TSH) levels as a measure of risk of the development of nodular thyroid disease and, if such occurs, for an aggressive surgical approach. There exists a growing population at risk attributable to the success of radiation treatment of Hodgkin's and pediatric head and neck tumors. The question is raised regarding the theoretical benefits of thyroid suppressive therapy in this group at risk. With the instructive case presented, radical surgery for either thymic or thyroid carcinoma and careful monitoring for decades-late local recurrences of thymoma are suggested.

Adult↗
PubMed1992

Laser thoracoscopy for pleural effusion.

A potential, new, therapeutic modality for the treatment of recurrent symptomatic pleural effusion in a patient with metastatic carcinoma is presented using "minimal access surgery." Diagnosis at the time of thoracoscopy, as well as treatment using free-beam and contact-tip modalities, is outlined in detail. Also, a complication of inter-costal artery bleeding is presented, as well as its solution using the end-firing endoclip applier. This is an effective and useful procedure that should be particularly of interest to surgeons already using various scope methods. Surgeons currently express strong interest in accomplishing diagnosis and treatment goals in a variety of clinical situations using "minimal access surgery," a phrase coined at the 1989 International Congress of the Society of American Gastrointestinal and Endoscopic Surgeons. Enthusiasm about this procedure is evident across the country by the number of laparoscopic courses offered at a variety of institutions. Similarly, the chest allows certain applications of minimal access surgery resulting in accurate diagnosis and possible definitive treatment by use of the thoracoscope.

Aged↗
PubMed1985

Changes in the surgical treatment of acid peptic disease.

The surgical treatment of acid peptic disease at Hennpin County Medical Center (Minneapolis, MN) during two time periods separated by a 12-year interval was reviewed. In comparing the more recent period with the earlier, the following was observed: 1) total number of operations decreased by one-third, but the number of emergency operations was the same; 2) overall operative mortality did not change even though more patients in the recent period had associated systemic disease; 3) the location of ulcers did not change; 4) hemorrhage, as an indication for emergency surgery, increased both relatively and absolutely; and 5) the preferred surgical procedure during both periods was vagotomy and antrectomy, but vagotomy and drainage was done with increased frequency in the more recent period. During both time periods, emergency surgery was associated with almost a tenfold increase in operative mortality.

Drainage↗