Functional proteins coded by genes 46 and 47 are required for (i) continuation of deoxyribonucleic acid (DNA) synthesis in the late period of T4 infection and (ii) production of normal, late replicating DNA which contains strands with a sedimentation coefficient in alkaline sucrose greater than that of mature DNA (73S). Continued DNA synthesis in the late period in the absence of functional genes 46 or 47 can be achieved by inhibiting late protein synthesis either by using bacterio-phage with a second mutation in gene 55 or by adding chloramphenicol to the culture before the decline in the rate of DNA synthesis. However, when functional 46/47 proteins are absent throughout infection, no strands with a sedimentation coefficient greater than 73S (in alkaline sucrose) are produced. This is the case even when DNA synthesis is allowed to continue. DNA arrest is accompanied by conversion of rapidly sedimenting, replicating DNA to slower sedimenting forms. When 46/47 is absent from the beginning of infection, the conversion product has a smaller sedimentation coefficient than mature DNA both in neutral and alkaline sucrose. When DNA arrest occurs midway in infection by heat-inactivating the ts46 enzyme, the conversion product has a sedimentation coefficient (i) the same as mature DNA in both neutral (63S) and alkaline sucrose if capsid assembly is allowed to take place and (ii) close to 63S in neutral sucrose but heterogenous and relatively greater (up to 100S) in alkaline sucrose if capsid assembly is inhibited. The structure of this DNA is unknown.

Centrifugation, Density Gradient↗

PubMedDate not supplied

Modification of polyetherurethane for biomedical application by radiation induced grafting. II. Water sorption, surface properties, and protein adsorption of grafted films.

A series of polyetherurethane films grafted by means of gamma radiation with hydrophilic or reactive monomers (2-hydroxyethyl methacrylate, 2,3-epoxypropyl methacrylate, 2,3-dihydroxypropyl methacrylate, and acrylamide) and partially chemically modified were subjected to various physico-chemical investigation methods involving water sorption, contact angle, and protein adsorption measurements. From contact angle data the interfacial free energy gamma sw between grafted films and water was calculated. It was found that the water uptake of grafted films increases with grafting yield or, in the case of grafted and afterwards chemically modified films, with reaction yield; the diffusion coefficient of water in the modified films also increases with grafting yield. Contact angle studies revealed all grafted films to have surfaces more hydrophilic than the ungrafted trunk polymer. The degree of hydrophilicity--especially of HEMA-grafted films--strongly depends on grafting conditions. For some grafted samples with high surface hydrophilicity very low interfacial free energies approaching zero were measured. The study of the competitive adsorption of bovine serum albumin, gamma-globulin, and fibrinogen from a synthetic protein solution onto modified films showed that the adsorption of albumin increases markedly with increasing grafting yields, whereas the fibrinogen and gamma-globulin adsorption only slightly increases. A correlation between interfacial free energy and protein adsorption in the sense of the "minimum interfacial free energy hypothesis" was found only for samples with grafting yields below 5%. At higher grafting yields the increased surface area complicates the analysis.

Adsorption↗

PubMedDate not supplied

Modification of polyetherurethane for biomedical application by radiation-induced grafting. I. Grafting procedure, determination of mechanical properties, and chemical modification of grafted films.

Radiation grafting of monomers onto suitable trunk polymers is a useful tool for tailoring new polymers for special purposes. This technique has been used in the past for the development of biocompatible materials, e.g., by grafting hydrogels onto mechanically stable polymers. In this first part of our work, the radiation grafting of hydrophilic or reactive monomers onto a polyetherurethane film using the pre-swelling technique is described. Following this technique the trunk polymer was swollen in the monomer before irradiation. As monomers 2-hydroxyethyl methacrylate (HEMA), 2,3-epoxypropyl methacrylate (GMA), 2,3-dihydroxypropyl methacrylate (GOMA), and acrylamide (AAm) were used. The kinetics of the grafting reactions were examined, and the distribution of the graft component inside the trunk polymer was investigated by means of infrared (IR) spectroscopy. Surface-grafted as well as bulk- and surface-grafted products could be obtained. The mechanical behavior of the grafted films--especially in the water-swollen state--was examined and compared with that of the pure trunk polymer. In nearly all cases it was found that the tensile strength sigma B and the elongation at break epsilon R decreases as the grafting yield increases. Modification of GMA- and AAm-grafted films via chemical reactions was performed to create new functional groups of biomedical interest. In this manner a diol structure, a carboxylic acid structure, and a sulfonic acid group could be introduced in the grafted polymer. The water uptake of such modified films is increased markedly when compared with that of the unmodified samples.

Biocompatible Materials↗

PubMedDate not supplied

Pharmacokinetics and pharmacodynamics of the novel H1-receptor antagonist emedastine in healthy volunteers.

OBJECTIVE: Emedastine is a novel H1-receptor antagonist with pre-clinically well-documented anti-allergic effects. Here, we set out to study the relationship between emedastine pharmacokinetics and the suppressive effect on histamine-induced wheals and flares, and to compare these effects to placebo and cetirizine. METHODS: Emedastine (4 mg q.d.), emedastine (2 mg b.i.d.), cetirizine (10 mg q.d.) and placebo were administered to healthy volunteers in a double-blind, cross-over fashion. On day 1 and day 5 (steady state) following drug administration, wheals and flares were induced by skin-prick testing with 1 mg ml(-1) or 10 mg ml(-1) histamine. RESULTS: Following the administration of 4 mg emedastine q.d., mean area under the concentration-time curve (AUC)0-24 values of 34.49 +/- 24.07 ng h ml(-1) and 47.05 +/- 36.12 ng h ml(-1) were attained on day 1 and day 5, respectively. Following the administration of emedastine (2 mg b.i.d.) mean AUC0-24 values were 29.75 +/- 19.92 ng h ml(-1) and 46.13 +/- 38.50 ng h ml(-1) on day 1 and day 5, respectively. Histamine-induced wheals and flares were significantly more effectively suppressed by emedastine and cetirizine than placebo. At pharmacokinetic steady-state levels, no significant difference could be found in the potency between cetirizine and emedastine (2 mg b.i.d.). CONCLUSION: Emedastine displays pharmacodynamic properties comparable with cetirizine and therefore qualifies as a safe and alternative compound with H1-receptor antagonist properties. Additional larger studies may be needed to substantiate potential benefits of cetirizine over emedastine after single-dose administration.

Adult↗

PubMedDate not supplied

Bacterial adherence to hydrophilic polymer-coated polyurethane stents.

Biliary stent blockage by adherence of bacteria and formation of biofilm is a major problem in endoscopic stenting procedures. We have investigated bacterial adherence to hydrophilic polymer (Hydromer)-coated polyurethane stents in stationary and perfusion experiments. Adherence of gram negative and gram positive organisms under stationary conditions was similar between Hydromer-coated and non-coated control polyurethane stents; however, a marked 1 to 3 log reduction in adherence to Hydromer-coated stents occurred when perfusion experiments in phosphate buffer solution or bile were performed. The results suggest that Hydromer-coated polyurethane stents could be useful in preventing complications caused by biliary stent blockage.

Bacterial Adhesion↗

PubMedDate not supplied

[Chronic liver disease after treatment of malignancies in children].

Chemotherapy, which has greatly improved the prognosis of children with malignant diseases, is potentially hepatotoxic. Furthermore, there is a risk for viral hepatitis acquired by blood products. In this study we looked for hepatotoxicity and for chronic viral hepatitis during and after chemotherapy in 50 unselected children with malignant diseases. 29 children had been treated for leukemia or lymphoma, 19 for solid tumors, 2 for histiocytosis. All patients had been treated before 1991 and had received blood products not screened for hepatitis C-antibodies. In 18 girls and 32 boys aged 12.3 years (range 6.7-24.5 years) hepatitis B- and hepatitis C-serology and liver function tests were measured during a routine check-up 3.6 years (range 0.5-11.8 years) after the last chemotherapy. Liver function tests during chemotherapy were reviewed retrospectively. During chemotherapy 86% of children showed increased ALT and AST levels, 10% had levels above 500 U/l. At follow up 16 children (32%) had pathological liver function tests, especially slightly increased AST and ALT, 13 of these 16 patients had chronic hepatitis C. In contrast only 2 of 34 patients with normal liver function tests had a viral hepatitis (p = 0.001). Patients with elevation of AST and ALT above 100 U/l during chemotherapy had significantly more often a viral hepatitis than those with normal or slightly elevated aminotransferases. Our study shows that hepatocellular damage is a frequent complication following chemotherapy. However this progresses to chronic liver disease very rarely unless the patient acquired a viral hepatitis. The prevalence of chronic hepatitis C was very high in our patients. As screening of blood products for hepatitis C-antibodies is routinely performed since 1991 this problem is likely to have decreased.

Adolescent↗

PubMedDate not supplied

[Anesthesia and resuscitation in surgery of scoliosis, with the Harrington operation].

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Abnormalities, Multiple↗

PubMedDate not supplied

Technetium-99m-tetrofosmin: a new agent for melanoma imaging?

The aim of our study was to examine whether technetium-99m 1,2-bis[bis(2-ethoxyethyl) phosphino]ethane (tetrofosmin) a lipophilic, cationic tracer which was first developed for myocardial perfusion imaging, could be a new radiopharmaceutical for melanoma imaging. We therefore used two human cell lines, SK-MEL 28 and 5i8 A2 (n = 6, cell concentration 106/ml, incubation at 22 degrees C and 37 degrees C, 50-100 approximately lCi/ml Tc-99m-tetrofosmin, time of incubation 10-180 minutes). The cellular uptake by both cell lines was determined. In contrast to another non- melanoma tumor cell line MCF-7 (a human adenocarcinoma breast cancer) which reached steadystate almost immediately (within 10 minutes), the cellular uptake of SK-MEL-28 increased after 60 minutes and showed a very high uptake (> 10%) after 120 minutes and decreased after 180 minutes (6-8%), while the uptake in 518 A2 cells was about 5% after 90 minutes. Our data show that Tc-99m-tetrofosmin could be a promising agent for melanoma imaging.

Biological Transport↗