Improvement of plasma lipoprotein profiles during high-flux dialysis

Patients undergoing maintenance hemodialysis therapy have increased mortality due to cardiovascular disease. One possible etiologic factor for this increased mortality is the lipid abnormalities associated with chronic renal failure. These include elevated triglyceride (TG) and decreased high-density lipoprotein (HDL) concentrations. Lipoprotein profiles of patients undergoing chronic hemodialysis with either saponified cellulose ester (CE) (N = 9) or polysulfone (PS) high-flux dialysis membranes (N = 10) were compared. Patients in each group received similar amounts of heparin during the dialysis. CE-dialyzed patients showed no alteration in serum TG, HDL, low-density lipoprotein, or total cholesterol when predialysis and postdialysis values were compared. PS patients, on the other hand, had a significant decrease in TG concentrations (P < 0.01) as well as a significant rise in HDL (P < 0.01). These changes might signify activation of lipoprotein lipase (LPL) during dialysis. LPL activity in PS sera was significantly greater than LPL in CE sera. Moreover, sera from PS patients inhibited LPL much less than did sera from CE patients. These findings suggest that a circulating substance not dialyzable with cellulosic membranes inhibits LPL in uremic subjects and is removed during dialysis with a PS membrane. Alternatively, the greater biocompatibility of PS may produce less LPL inhibitory cytokines during dialysis. The improvement of lipoprotein profiles in patients receiving dialysis with PS membranes may, in the long term, lead to less morbidity and mortality from atherosclerotic disease.     

A histological and ultrastructural study of the cells of the mantle edge of a marine bivalve, Cerastoderma edule

The cells of the mantle edge of Cerastoderma edule are described after light and electron microscopical observations. Histochemical tests for calcium in the mantle edge and digestive gland (Dahl, 1952; McGee-Russell, 1958) and analytical electron microscopy of mantle edge of C. edule both failed to show calcium. Similar results were obtained for Mytilus edulis and Chlamys opercularis. However, calcium was detected in the digestive gland of the terrestrial gastropod Helix aspersa. The outer secretory fold of the mantle edge is composed of tall columnar cells. These cells have highly convoluted lateral cell membranes with which many mitochondria are closely associated. These features are indicative of an ion pump which could move calcium from the mantle space to the extrapallial cavity (compare with Bubel's findings, 1973b). There are many features of the cells lining the periostracal groove of C. edule that have not been reported previously (e.g. Bubel, 1973b) and which are now discussed. The periostracal sheet arises within a line of basal cells in the fundus of the periostracal groove. Within these cells the periostracum in section has a spiral form. It is suggested that the newly formed periostracum adheres to the microvillous border through secretions produced from the middle fold cells lining the groove. During its passage along the groove the periostracum is gradually thickened by secretions from the outer fold cells.     

A frequent activated smoothened mutation in sporadic basal cell carcinomas

Basal-cell carcinomas (BCCs) are the most common cancer in Caucasians. It has been reported that the patched gene is inactivated in 30-40% sporadic BCCs and 20% sporadic medulloblastomas via loss of heterozygosity and nonsense mutations. Recently, two activating smoothened mutations have been found in the sporadic basal cell carcinomas. One, at base pair 1604 (G-to-T transversion) of exon 9, changes codon 535 from tryptophan to leucine, and the other, at base pair 1685 (G-to-A transition) of exon 10, changes codon 562 from arginine to glutamine (Xie et al., 1998). In our study, 1604G-->T was found in 20 out of 97 (20.6%) sporadic BCCs. The high prevalence indicates that 1604G is the mutation hot spot in our tumor samples. This mutation was detected in all three histological subtypes of BCCs, suggesting that smoothened mutation is an early event during the development of the tumor. Our finding of a high smoothened mutation rate, together with high frequent patched gene mutations reported recently, indicates that activation of the hedgehog signal transduction pathway is the most common and early event in the development of sporadic BCCs. Additionally, to determine whether smoothened, like patched, is also involved in the carcinogenesis of medulloblastomas, we screened medulloblastoma samples for these two mutations by restriction analysis. We have found the 1604G-->T mutation in 1 out of 21 medulloblastomas. This result confirmed smoothened gene involvement in the carcinogenesis of medulloblastoma.     

Dynamic equilibrium unfolding pathway of human tumor necrosis factor-alpha induced by guanidine hydrochloride

The dynamic equilibrium unfolding pathway of human tumor necrosis factor-alpha (TNF-alpha) during denaturation at different guanidine hydrochloride (GdnHCl) concentrations (0-4.2 M) was investigated by steady-state fluorescence spectroscopy, potassium iodide (KI) fluorescence quenching, far-UV circular dichroism (CD), picosecond time-resolved fluorescence lifetime, and anisotropy decay measurements. We utilized the intrinsic fluorescence of Trp-28 and Trp-114 to characterize the conformational changes involved in the equilibrium unfolding pathway. The detailed unfolding pathway under equilibrium conditions was discussed with respect to motional dynamics and partially folded structures. At 0-0.9 M [GdnHCl], the rotational correlation times of 22-25 ns were obtained from fluorescence anisotropy decay measurements and assigned to those of trimeric states by hydrodynamic calculation. In this range, the solvent accessibility of Trp residues increased with increasing [GdnHCl], suggesting the slight expansion of the trimeric structure. At 1.2-2.1 M [GdnHCl], the enhanced solvent accessibility and the rotational degree of freedom of Trp residues were observed, implying the loosening of the internal structure. In this [GdnHCl] region, TNF-alpha was thought to be in soluble aggregates having distinct conformational characteristics from a native (N) or fully unfolded state (U). At 4.2 M [GdnHCl], TNF-alpha unfolded to a U-state. From these results, the equilibrium unfolding pathway of TNF-alpha, trimeric and all beta-sheet protein, could not be viewed from the simple two state model (N-->U).     

Polymer electrolyte membranes from fluorinated polyisoprene-block-sulfonated polystyrene: Structural evolution with hydration and heating

Small-angle neutron scattering (SANS) and ultra-small-angle X-ray scattering (USAXS) have been used to study the structural changes in fluorinated polyisoprene/sulfonated polystyrene (FISS) diblock copolymers as they evolved from the dry state to the water swollen state. A dilation of the nanometer-scale hydrophilic domains has been observed as hydration increased, with greater dilation occurring in the more highly sulfonated samples or upon hydration at higher temperatures. Furthermore, a decrease in the order in these phase separated structures is observed upon swelling. The glass transition temperatures of the fluorinated blocks have been observed to decrease upon hydration of these materials, and at the highest hydration levels, differential scanning calorimetry (DSC) has shown the presence of tightly bound water. A precipitous drop in the mechanical integrity of the 50% sulfonated materials is also observed upon exceeding the glass transition temperature (T_g), as measured by dynamic mechanical analysis (DMA).     

The unlubricated wear of sintered steels

The unlubricated wear of 10.3% porosity sintered medium-carbon and 12.8% porosity sintered low-alloy steels was investigated under different sliding conditions. Their wear characteristics were found to be similar to their non-sintered counterparts. Within this range of sliding conditions, both mild-oxidational and delamination wear took place, with the former dominating the wear processes. The oxide debris produced changed with the applied load: switching from a low-temperature oxide to a high-temperature one at higher loads. The wear rates agreed reasonably well with Archard's law and with data from other sources, suggesting that Archard's law can account for the wear rates produced by both mild-oxidational wear and delamination wear. This agreement also suggests that within the range of porosites investigated an overall framework can be established in the unlubricated wear of both sintered and non-sintered steels.     

In vivo verification of an automatic noninvasive system for real time Kt evaluation

It is generally accepted that morbidity and mortality of hemodialysis patients is related to dialysis quantitation. Currently available methods for the quantitation of dialysis require blood sampling or a continuous measurement of changes in urea concentration during treatment. These maneuvers are time consuming and expensive, and are generally performed, at most, once per month. The authors introduce an on-line, automated method for measurement of dialyzer electrolyte clearance comparable to urea clearance by using dialysate conductivity sensors placed pre and post dialyzer, and measuring conductivity at three different pre dialyzer levels. Conditions that reduce clearance, such as recirculation or fiber clotting, are automatically taken into account so that the method measures effective clearance rather than dialyzer clearance. In vitro and in vivo studies validate the method. Results are immediately available and can be used to address problems such as improper needle placement and access recirculation. In addition, repetitive electrolyte clearance data can serve to enhance quality assurance programs with respect to verifying the function of reused or new dialyzers. Appropriate algorithms can be used to calculate delivered Kt/V.