Exploring the liquid-like layer on the ice surface.

Using interfacial force microscopy and a spherical glass probe, we investigate the adhesive and mechanical properties of the so-called liquid-like layer (L-LL) on the surface of ice at various temperatures over the range from -10 to -30 degrees C. We find that the layer thickness closely follows that predicted on thermodynamic grounds, while the adhesive interaction has the behavior of a "frustrated capillary", strongly suggesting that the layer is viscoelastic. This viscoelasticity is directly probed using a lateral-dither technique to obtain information on the layer's viscous response as a function of both temperature and interfacial separation.

Nanomechanical contrasts of gel and fluid phase supported lipid bilayers.

Lipid bilayers exhibit structural diversity that contributes to the complex properties of the cell membrane. We use interfacial force microscopy to correlate mechanical properties with the two-dimensional phase behavior of supported lipid bilayers (SLBs). Upon indentation by a 500 nm tungsten tip, a contrast in the mechanical response is observed for gel vs fluid phase SLBs. We measure the yield force and time scale for recovery for these films. Consistent with a gel phase, a DSPC SLB has a relatively high yield force and slow recovery. In the higher mobility fluid phase, a DLPC SLB has a lower yield force and completely recovers within the experimental time scale. Friction measurements offer further contrast between the two SLBs.

Intraocular epiretinal prosthesis to restore vision in blind humans.

Visual sensations in blind patients suffering from retinal degenerations may be restored by electrical stimulation of retinal neurons using implantable microelectrode arrays. The EPI-RET-3 project was initiated to evaluate a wireless intraocular retinal implant system for human use in terms of safety and efficiency. The implant is a remotely controlled fully intraocular prosthesis consisting of a receiver and a stimulator module. The stimulator is placed onto the retina's surface. Data and energy are transmitted via an inductive link from outside the eye to the implant. The EPI-RET-3 device was implanted into six legally blind patients with Retinitis Pigmentosa (RP) for a period of four weeks. The surgery was performed without complications. The implants were activated on days 7, 14 and 27 after implantation. All patients reported visual sensations such as dots, arcs, or lines of different colours and intensities. The required stimulation thresholds were found to be very low. Implantation of the wireless EPI-RET-3 device is safe and the system is suitable to elicit visual sensations in blind RP patients. Major problems in the design and fabrication of a prosthesis for artificial vision could be solved in this approach.

Density dependent friction of lipid monolayers.

We measure frictional properties of liquid-expanded and liquid-condensed phases of lipid Langmuir-Blodgett monolayers by interfacial force microscopy. We find that over a reasonably broad surface-density range, the friction shear strength of the lipid monolayer film is proportional to the surface area (42-74 A2/molecule) occupied by each molecule. The increase in frictional force (i.e., friction shear strength with molecular area can be attributed to the increased conformational freedom and the resulting increase in the number of available modes for energy dissipation.

Development of an inductively coupled epiretinal vision prosthesis.

Electrical stimulation of the retina elicits visual perception in patients with retinitis pigmentosa. Using the potentials of microsystem technology, neural prostheses to restore vision become feasible that are completely implantable in the eye. In this paper, we describe the development of an inductively coupled epiretinal vision prosthesis. Microelectronic chips for data encoding and stimulation were assembled on flexible substrates with an integrated electrode array. The system was encapsulated with parylene C and silicone rubber. The receiver part was placed into an artificial intraocular lens. Microcables led to the stimulation array in the macula region. This prototype elicited spatio-temporal patterns in the visual cortex after electrical stimulation of the retina in the cat.

The phenylalanine loading test in the differential diagnosis of dystonia.

Early diagnosis of dopa-responsive dystonia (DRD) and its delineation from other dystonic syndromes is of great relevance because DRD is an eminently treatable condition. The possible relevance of the phenylalanine loading test (Phe-L) in differentiating DRD from primary focal and generalized dystonia was investigated. A marked difference in the phenylalanine/tyrosine ratio between patients with DRD and patients with other types of dystonia was observed. This indicates that Phe-L may be helpful in the differential diagnosis of dystonias.

The efficacy of 2',2'-difluorodeoxycytidine (gemcitabine) and vinblastine combined with interferon in nude mice xenografts of human renal cell carcinoma.

Recent in vitro experiments indicated strong activity of 2',2'-difluorodeoxycytidine (dFdC, gemcitabine) in human renal cell carcinoma (RCC) cell lines and an increase of efficacy by combined application of interferon (IFN). In the present study, nude mice with xenografts from ACHN- or SN12C cells were treated by dFdC, dFdC plus IFN-alpha or vinblastine (VBL) plus IFN-alpha. ACHN-xenografts were significantly more inhibited by dFdC+/-IFN-alpha than by VBL+IFN-alpha. Complete remissions (CR) were only seen by dFdC. An additional treatment with IFN-alpha shortened the time to commencement of tumor remission and increased CR of ACHN- and SN12C-tumors (40%; 7%) compared to a treatment with dFdC alone (20%; 0). dFdC+IFN-alpha reduced the number of pulmonary metastases compared to untreated animals. Survival was significantly prolonged by dFdC+/-IFN-alpha in ACHN-mice and dFdC+IFN-alpha or VBL+IFN-alpha in SN12C mice. In conclusion, experimental data confirm dFdC as a superior drug against human RCC compared to VBL. Combined therapy with IFN-alpha increased the efficacy of dFdC in terms of tumor response in immunodeficient nude mice, thus clinical studies are strongly recommended in patients with metastatic renal cell carcinoma.

Interferon-alpha and gemcitabine (2',2'-difluorodeoxycytidine) in adult and pediatric renal tumors.

2',2'-difluorodeoxycytidine (dFdC) is an active anticancer drug in different human malignancies. The present study aimed to evaluate if the activity of dFdC in renal tumors could be improved by interferon-alpha (IFN-alpha). The influence of IFN-alpha (4 h) on the cytotoxicity of dFdC was analyzed in vitro by a colorimetric assay. in vivo, nude mice with xenografts from human nephroblastoma (AC-KLxe-12) and renal cell cancer (ACHN, SN12C) were treated by dFdC +/- IFN-alpha. IFN-alpha alone resulted in no growth inhibition in vitro, but pretreatment with IFN-alpha sensitized SN12C and ACHN cells against dFdC. The additional treatment with IFN-alpha increased the CR rate of ACHN- and SN12C-mice (40%; 7%) compared to dFdC alone (20%; 0%). Xenografts from AC-KLxe-12 did all progress. In conclusion, IFN-alpha increased cytotoxicity of dFdC in vitro and tumor responses of renal cell cancer (RCC) in xenografts. Since therapy lacked activity in nephroblastoma, further studies should focus on RCC to compare the efficacy of dFdC and interferons with other types of biochemotherapy.

Prognostic indicators for acute low-back pain.

Chart review was conducted on a 6-month sample of patients with low-back to identify outcome indicators in acute low-back pain. Two hundred seven episodes were identified. Extracted material included the age, sex, past history, time to presentation, occupation, suggested precipitating event of injury, and estimated difficulty of job tasks. Symptoms and findings presentation were also recorded. All cases were work-related, and the outcome indicator was time loss from work. Analysis of variance showed significant associations in time loss from work with factors including the occupation, age, job difficulty, past history, symptoms, examination, and diagnosis on presentation.

Comparison of the hypocholesterolemic effects of dietary soybean protein with those of formaldehyde-treated casein in rabbits.

Treatment of casein with formaldehyde changes its tertiary structure and decreases its hypercholesterolemic properties in rabbits. To investigate whether formaldehyde-treated casein exerts this hypocholesterolemic effect in the same manner as soybean protein, rabbits were fed high or low cholesterol diets containing soybean protein, casein, formaldehyde-treated casein or a mixture of casein and formaldehyde-treated casein. Formaldehyde-treated casein was hypocholesterolemic when fed in a low, but not in a high, cholesterol diet. The hypocholesterolemic effect of soybean protein was independent of the amount of cholesterol included in the diet. In contrast to rabbits fed soybean protein, steroid absorption in those fed formaldehyde-treated casein did not differ from that in rabbits fed native casein. Furthermore, the absorption of phosphorus and nitrogen was lower in rabbits fed formaldehyde-treated casein than in those fed native casein, whereas the absorption found in rabbits fed soybean protein resembled that of their casein-fed counterparts. The diets containing soybean protein and formaldehyde-treated casein produced a comparable ratio of lysine to arginine in serum. The results presented in this paper indicate that the hypocholesterolemic action of dietary formaldehyde-treated casein does not resemble that of soybean protein.

Modulating effects of beta-naphthoflavone on the induction of SCEs by model compounds with emphasis on benzo[a]pyrene.

The inducing capability of the synthetic flavonol beta-naphthoflavone (beta-NF) on cytochrome P-450 content was studied in primary chick embryo hepatocytes. In addition, the modulating effects of pretreatment with beta-NF on the induction of sister-chromatid exchanges (SCEs) in V79 cells by mutagens from different chemical classes were investigated in a co-cultivation system consisting of primary chick embryo hepatocytes and V79 Chinese hamster cells. Finally, the effects of pretreatment on benzo[a]pyrene (B(a)P) metabolism were studied in more detail. Pretreatment of cultured primary chick embryo hepatocytes with beta-NF resulted in a large increase in cytochrome P-450 content (a 2.8-fold increase after 31 h). Pretreatment with beta-NF had no effect on the level of SCEs induced by N-nitroso-dimethylamine (NDMA) and 2-aminoanthracene (2AA). Pretreatment with beta-NF resulted in a decrease in B(a)P-induced SCEs. This inhibitory potential was positively related to the beta-NF dose. However, there was an inverse relationship between the inhibitory action of beta-NF and the dose of B(a)P, at higher doses less inhibition was observed. When beta-NF was applied simultaneously with B(a)P the percentage of decrease was about the same as for pretreatment. Pretreatment with beta-NF followed by simultaneous application of beta-NF and B(a)P did not result in larger effects. In addition, subcellular fractions were prepared from chick embryos pretreated with beta-NF in ovo. The use of the S9 fraction resulted in a large decrease (80%) in the induction of SCEs in V79 cells by B(a)P whereas the use of the microsomal fraction resulted in a 70% increase in SCE induction compared with non-pretreated microsomes. Pretreatment with beta-NF in ovo gave rise to a large increase in aryl hydrocarbon hydroxylase (AHH) activity in the hepatic microsomal fraction. Increases were observed in the formation of all B(a)P metabolites. In particular the formation of the proximate carcinogenic and mutagenic metabolite B(a)P-7,8 dihydrodiol was increased 7-fold. The data strongly suggest that the inhibitory effects of pretreatment of cultured primary chick embryo hepatocytes with beta-NF cannot be ascribed to its inducing capabilities but instead seem to be due to the formation of an intracellular pool of beta-NF which acts as a competitive inhibitor for B(a)P metabolism.