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Biomedical subjects

M Winter

Publications and source records attributed to M Winter.

At least 127 records · Page 7Linked to original sources

Experimental intraocular tolerance to liquid perfluorooctane and perfluoropolyether.

Three kinds of perfluorinated liquids (a perfluorooctane and two perfluoropolyethers) were evaluated as vitreous replacements. Tolerance to these liquids in rabbit eyes was investigated for periods of up to 2 months. Clinically, droplet formation of the liquids occurred within a few days of intravitreal injection. Histologic examination revealed no pathologic retinal changes 8 hours after surgery. At 6 days after surgery, hypertrophy of the Müller cells with bumplike protrusions into the interphotoreceptor space could be observed. At 1 month after surgery, light and electron microscopic examination showed larger droplike protrusions of Müller cells related to localized foldings of the outer retinal layers and rarefication of photoreceptor nuclei and loss of outer segments. Frequently disarranged, granule-loaded macrophages appeared in these areas. At 2 months after surgery, vesicles with low electron density appeared in some areas at the border between receptors and retinal pigment epithelium. In other areas pigment epithelial cells showed distinct hypertrophy (with drusen) toward the droplike Müller cell protrusion, together with narrowing of the interreceptor space. These findings were almost totally confined to the lower part of the retina that had been in permanent contact with the liquids. No histologic differences were noted between perfluorooctane- and perfluoropolyether-injected eyes. The results suggest that the liquids are not candidates for long-term vitreous replacement, but may be suitable for short-term intraoperative use.

Animals↗

[Bacterial spondylitis caused by Haemophilus aphrophilus].

Four weeks after a slight scratch a 43-year-old man noted a severe back pain. Physical examination gave suspicion of a bacterial spondylitis. From the biopsy of the involved vertebral body Haemophilus aphrophilus was isolated under aerobic growth conditions.

Adult↗

Oxidants, ATP depletion, and endothelial permeability to macromolecules.

Oxidants can reversibly increase the permeability of endothelium to ions and macromolecules. Oxidants also deplete ATP in cultured endothelial cells. We asked if oxidant-mediated ATP depletion, alone, accounted for the effects of oxidants on endothelial permeability to macromolecules. When porcine pulmonary artery endothelial cells were exposed to 2.5 mmol/LH2O2, ATP was depleted to 31.7% +/- 1.8% of control within 15 minutes and was reduced to 23.1% +/- 2.0% of control after 30 minutes. To determine if this magnitude of ATP depletion could account for the oxidant-induced increase in endothelial permeability to macromolecules, we measured ATP in endothelial cells exposed to metabolic inhibitors of ATP production. We then measured the effects of these metabolic inhibitors on endothelial monolayer permeability to macromolecules. ATP levels were reduced to 44% +/- 4% of control by 12 mmol/L deoxyglucose (DOG) in the absence of glucose and to 2% +/- 1.3% of control by DOG with 25 nmol/L antimycin A in the absence of glucose. Reduction of endothelial cell ATP to these levels with the metabolic inhibitors did not alter the flux of albumin or dextran across the endothelial monolayers. Thus ATP depletion, by itself, does not explain oxidant-induced changes in endothelial permeability to macromolecules.

Adenosine Triphosphate↗

Influence of human transferrin and group-specific protein on endotoxicity in vitro.

The present study concerns the endotoxin neutralizing activity of human iron-free transferrin, and group-specific protein also called Gc-globulin. Iron-free transferrin was used because former studies showed that the endotoxin binding capacity is restricted to apotransferrin. The endotoxin neutralizing activity of the different protein preparations was tested by use of the limulus-amebocyte-lysate test after solubilizing in an isotonic electrolyte buffer at pH 7.0. Surprisingly, in the presence of transferrin the limulus test detected about 200% and 150%, respectively, of the endotoxin content measurable in the presence of human albumin or without any protein. The addition of Gc-globulin leads to a loss of endotoxin of about 40%.

Albumins↗

The conductance of cultured epithelial cell monolayers: oxidants, adenosine triphosphate, and phorbol dibutyrate.

Oxidants are one class of inflammatory molecules that may contribute to an increase in epithelial permeability to water and solutes that commonly occurs during acute inflammation. We and others have observed that oxidants reversibly alter the paracellular conductance of Madin Darby canine kidney epithelial (MDCK) cell monolayers. The mechanism by which oxidants reversibly alter MDCK monolayer conductance is not yet fully understood. Some investigators have suggested that oxidants might alter MDCK monolayer paracellular conductance by depleting adenosine triphosphate (ATP) in the cells. When we exposed MDCK cells to doses of oxidants that increased monolayer paracellular conductance in earlier studies, ATP was depleted within 10 min. However, when ATP was depleted to similar levels with an inhibitor of glycolytic ATP production, 2-deoxy-D-glucose (DOG), monolayer paracellular conductance was not increased. Severe ATP depletion with DOG and the mitochondrial metabolic inhibitor, antimycin A (AA), had very limited, ATP-independent effects on paracellular conductance. As an alternative explanation for the effects of oxidants on MDCK monolayer paracellular conductance, we had reported that oxidants increased production of inositol phosphates and diglycerides in MDCK cells. Synthetic diglyceride and phorbol dibutyrate (PDBU) increased MDCK monolayer conductance to ions and mannitol in earlier studies. When MDCK cell ATP was depleted with DOG (to the level caused by oxidants), the increase in conductance following PDBU was not different from that observed in control cells. More severe ATP depletion, with DOG and AA, prevented the increase in conductance following PDBU.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine Triphosphate↗

Results of screw osteosynthesis in spondylolysis and low-grade spondylolisthesis.

Nineteen patients with spondylolysis and low-degree spondylolisthesis were treated with bone grafting and osteosynthesis of the pars defect with the Morscher hook screw (16 cases) or with Buck's procedure (three cases). Eighteen patients had a follow-up examination. In the age-group 9-16 years (ten patients) there were 80% excellent or good results with fusion, whereas in the adult group (eight cases) the majority had poor results. It seems that the operative techniques which we applied are useful in juvenile patients; adults require a more reliable fixation.

Adolescent↗

[Preoperative autologous blood deposit and liquid storage for replacement arthroplasty].

Transfusion of homologous blood components is associated with immunological (incompatibility, alloimmunization, immunosuppression) and infectious risks (hepatitis, cytomegalovirus, HIV and other agents). Endoprosthetic surgery of the hip and knee frequently requires transfusion. Preoperative deposit of autologous blood can reduce homologous transfusion requirements. The simplest method is liquid storage of whole blood. In order to re-examine the efficiency of our present scheme of preoperative deposit, we studied patients scheduled for endoprosthetic surgery with respect to the amount of blood deposited, stimulation of erythropoiesis, and homologous blood requirements at the time of operation. PATIENTS AND METHODS. Sixty-seven consecutive patients (33 men, 34 women) scheduled for endoprosthetic replacement of hip or knee or for revision arthroplasty of the hip were studied. Patients with anemia, coagulopathies, coronary heart disease, severe obstructive or restrictive pulmonary disease, cerebral sclerosis, syncopes and seizures were excluded from preoperative deposit. Patients deposited 450 ml at weekly intervals, with occasionally slightly higher or lower volumes. A patient was temporarily deferred when the hemoglobin concentration prior to donation fell below 11 g/dl. Blood was collected in CPDA-1 buffer. The aim was a deposit of three units. In patients undergoing exchange reoperation of a total hip arthroplasty, intra- and postoperative autotransfusion with a cell separator was employed in addition to preoperative donation. RESULTS. The age of the patients ranged from 43 to 83 years (mean +/- SD: 61.2 +/- 9.1). The differences between men and women with respect to height (172.9 +/- 6.8 vs 160.6 +/- 7.4 cm; p less than or equal to 0.001), weight (75.7 +/- 11.2 vs 69.1 +/- 11.0 kg; p less than or equal to 0.05), calculated blood volume (p less than or equal to 0.001), and erythrocyte volume prior to donation (p less than or equal to 0.001) were significant. A total of 185 units was deposited. Men donated 1350 (450-1970) ml blood (median, range) and women 1260 (340-1450) ml (p less than or equal to 0.01). Hemoglobin concentrations decreased significantly from an average of 14.7 g/dl in men and 13.8 g/dl in women prior to donation to 13.4 g/dl and 12.3 g/dl preoperatively (p less than or equal to 0.0001 for both groups). The donation was not associated with serious complications. For 4 patients the scheduled operation was deferred for a longer term. Forty-six patients (23 men, 23 women) underwent total hip arthroplasty, 12 (4 men, 8 women) exchange of total hip arthroplasty, and 5 (3 men, 2 women) endoprosthetic knee surgery. In total hip arthroplasty men required 0 to 500 ml homologous packed red cells (median=0), women 0 to 1250 ml (median=0;p less than or equal to 0.05). Thirty-nine (69.6%) of the patients, 19 (82.6%) men and 13 (56.5%) women, did not require homologous transfusion.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗

Characterization of two different genes (cDNA) for cytochrome c oxidase subunit VIa from heart and liver of the rat.

By antibody screening of a rat liver and a rat heart cDNA library in lambda gt11 two clones coding for the liver- and heart-specific subunit VIa of rat cytochrome c oxidase were isolated. In the heart cDNA sequence a TAA stop codon was found in frame 18 bp 5' upstream of the first methionine codon, thus excluding a leader sequence for this protein. The two cDNAs contain the full-length coding region of two subunits. The amino acid sequences of the two subunits show only 50% homology, whereas 74% homology was found between rat heart and bovine heart subunit VIa. By Northern blot analysis it is shown that the gene for subunit VIa from heart is only expressed in heart and skeletal muscle, whereas that from liver is also expressed in kidney, brain, heart and weakly in muscle.

Amino Acid Sequence↗

Oxidants and conductance of cultured epithelial cell monolayers: inositol phospholipid hydrolysis.

Reactive oxidants contribute to the alterations in endothelial and epithelial permeability that characterize the inflammatory response. We previously noted that noncytolytic doses of oxidants reversibly decreased the electrical resistance across cultured monolayers of Madin-Darby canine kidney (MDCK) cells (J. Clin. Invest. 76: 1155-1168, 1985). In this investigation, we have found that similar doses of oxidants initiate inositol phospholipid hydrolysis by a phospholipase C in cultured MDCK cells, with resultant increases in inositol polyphosphates, phosphatidic acid, and 1,2 diglycerides. Activation of this pathway is linked to activation of protein kinase C in many cells. The addition of phorbol 12,13-dibutyrate (PDBU) and 1-oleoyl-2-acetyl-sn-glycerol, activators of protein kinase C, decreased the electrical resistance across MDCK monolayers cultured on micropore filters similar to the effects of hydrogen peroxide. In contrast, the addition of 4 alpha-phorbol 12,13-didecanoate, a chemically similar compound that does not activate protein kinase C, did not decrease the electrical resistance. When MDCK monolayers were exposed to PDBU, fixed, and stained with rhodamine phallicidin, the peripheral band of actin in the cells showed a loss of staining density and continuity similar to the changes in phallicidin staining we previously noted in cells exposed to hydrogen peroxide. These data are consistent with the hypothesis that some of the reversible effects of oxidants on epithelial barriers are mediated through phospholipase C hydrolysis of inositol phospholipids with consequent activation of protein kinase C.

Animals↗