Influence of labour on epidermal growth factor receptor distribution of the human chorion at term gestation

Ten patients with biopsy verified chronic hepatitis C virus (HCV) infection were treated with oral ribavirin at a dose of 1,000-1,200 mg per day in two divided doses for 12 weeks. Serum alanine aminotransferase (ALT) levels and hepatitis C viral ribonucleic acid (RNA) levels in serum were followed prior to, during, and 12 weeks posttreatment. ALT levels decreased significantly in all patients during therapy from a mean level of 3.21 mukat/l (range 1.22 to 7.79) before, to 1.25 mukat/l (range 0.78 to 2.04) at the end of treatment (P < 0.005). Hereafter, relapse to pretreatment levels was seen within 12 weeks after treatment stop. The hepatitis C viral RNA levels decreased from a mean 10 log titer of 4.1 (range 1-6) before treatment to 3.4 (range 1-5) at treatment stop. Five patients did not change their HCV RNA titers during treatment. Twelve weeks posttreatment only 3 patients had lower titers than prior to treatment. We conclude that oral ribavirin seems to reduce the viral load, at least temporarily, in some patients with chronic viremic HCV infection. Further studies are needed to evaluate fully the effect of oral ribavirin on chronic HCV infection.     

Kinetic analysis of papaya proteinase omega

Papaya proteinase omega (pp omega) has been purified from dried latex both by immunoaffinity and traditional methods. Kinetic analysis revealed that (1), the pp omega-catalysed hydrolysis of N-benzoyl-L-arginine p-nitroanilide (BApNA) has a lower specificity (kcat/Km) than the same reaction catalysed by papain; (2), the pp omega-catalysed hydrolysis of a tripeptide substrate having phenylalanine at the second position (S2-site) showed a more similar specificity to that catalysed by papain; (3), the significant difference between the two enzymes is that steady state kinetics with both L-BApNA and a tripeptide enables the identification in pp omega of other ionizations affecting binding. The active sites of papain and pp omega can therefore be distinguished by pH-dependence of kcat/Km.     

Korsakoff's syndrome, cognition and clonidine

Eighteen patients suffering from Alcoholic Korsakoff's Syndrome participated in a placebo-controlled double-blind cross-over trial of clonidine 0.3 mg b.d. for two weeks versus matched placebo for two weeks. A detailed neuropsychological assessment was carried out at the end of each treatment phase and staff ratings of behaviour were also obtained. Clonidine treatment resulted in no significant improvement over placebo on any of the cognitive measures employed. The results contradict previous smaller studies which had suggested that chronic treatment with clonidine had a memory-enhancing effect in Korsakoff's syndrome.     

Evaluation of hydroxylapatite/poly(l-lactide) composites: physico-chemical properties

The aim of this in vitro study was to examine the physico-chemical behaviour of hydroxylapatite/poly(l-lactide) (HA/PLLA) composites in solution tests. The polymer PLLA, the composites 30 wt% HA/PLLA (C30) and 50 wt% HA/PLLA (C50) and a one-side HA-coated PLLA (HAcP) were evaluated. Rectangular specimens were incubated in various acellular aqueous buffer solutions [citrate, Gomori's and phosphate-buffered saline (PBS)] up to 24 weeks. Data for cumulative release of calcium, phosphate and l-lactate release in solutions containing C30 or C50 showed linear patterns. Release data for solutions containing HAcP combined with scanning micrographs, X-ray microanalysis and X-ray diffraction patterns of the specimens in time showed that the plasma-sprayed HA coating on PLLA dissolves significantly, progressively in the first weeks and almost completely within the tested period of 24 weeks in vitro. A precipitate of scaly crystallites (calcium phosphates) was observed at the HA coating-PBS interface. After 24 weeks incubation all materials were still above their initial weight, indicating that swelling still exceeded dissolution. Application of C30, C50 and HAcP as implant materials seems interesting where initial stabilization through bone bonding is needed or where the linear release of constituents is a requirement. HAcP has the advantage that the HA coating acts as a hydrolysis barrier and consequently delays the degradation of PLLA in vitro.     

Mechanism for self-synchronization of femtosecond pulses in atwo-color Ti:sapphire laser

An experimental and theoretical analysis of the nonlinear coupling mechanism between the two solitary pulses circulating in a two-color femtosecond laser is presented. Two operation regimes; synchronized; and nonsynchronized; and a hysteresis of the transition between the two regimes are clearly observed; while independent modelocking and tunability of the output pulse trains is found in both regimes. Pulses in the range from 15 to 100 fs are synchronized with a timing jitter below 2 fs. The combined effects of cross-phase modulation and negative group velocity dispersion are shown to be responsible for the strong pulse correlation in the synchronized regime. Our experimental observations are in agreement with numerical simulations, thus confirming the theoretical model     

Luminol and lucigenin amplified chemiluminescence and lipidperoxidation with brain microsomes from rats during ontogenetic development

During the 1980s, the ecologic association of conjugated estrogens with endometrial cancer changed from positive to negative in a prepaid health plan. During the same period, use of progestins increased dramatically. We investigated whether the latter increase could explain the reversal of the estrogen-cancer association. Endometrial cancer incidence was estimated from cases recorded in the health plan registry divided by the number of women over age 45 years. Conjugated estrogens usage was measured as milligrams prescribed per woman per year and progestin was measured as tablets per woman per year, both based upon pharmacy records. Graphical and regression methods were used to analyze the resulting ecologic data. In a log-linear regression of incidence on conjugated estrogens and medroxyprogesterone usage, estrogen usage had a strong positive association with incidence, while medroxyprogesterone had a strong negative association with incidence. The change in the direction of the ecologic association between estrogen and endometrial cancer that occurred in 1984 continued until 1993, suggesting that the decline in endometrial cancer incidence and concomitant increase in conjugated estrogens usage since 1984 is explained by the increasing use of progestins. The data are entirely consistent with the hypothesis that progestins can protect against most of the excess risk conferred by conjugated estrogens, although the ecologic nature of the data prohibits drawing further inferences.     

Phosphoinositide 3-kinase induces scattering and tubulogenesis in epithelial cells through a novel pathway

Hepatocyte growth factor/scatter factor (HGF/SF) treatment of the Madin-Darby canine kidney epithelial cell line causes scattering of cells grown in monolayer culture and the formation of branching tubules by cells grown in collagen gels. HGF/SF causes prolonged activation of both the mitogen-activated protein (MAP) kinase extracellular signal-regulated kinase 2 (ERK2) and the phosphoinositide 3-OH kinase (PI 3-kinase) target protein kinase B (PKB)/Akt; inhibition of either the MAP kinase pathway by the MAP kinase/ERK kinase inhibitor PD98059 or the PI 3-kinase pathway by LY294002 blocks HGF/SF induction of scattering, although in morphologically distinct ways. Expression of constitutively activated PI 3-kinase, Ras, or R-Ras will cause scattering, but activated Raf will not, indicating that activation of the MAP kinase pathway is not sufficient for this response. Downstream of PI 3-kinase, activated PKB/Akt and Rac are both unable to induce scattering, implicating a novel pathway. Scattering induced by Ras or PI 3-kinase is sensitive to PD98059, as well as to LY294002, suggesting that basal MAP kinase activity is required, but not sufficient, for the scattering response. Induction of MDCK cell tubulogenesis in collagen gels by HGF/SF is inhibited by PD98059; expression of activated Ras and Raf causes disorganized growth in this system, but activated PI 3-kinase or R-Ras causes branching tubule formation similar to that seen with HGF/SF treatment. These data indicate that multiple signaling pathways acting downstream of Met and Ras are needed for these morphological effects; scattering is induced primarily by the PI 3-kinase pathway, which acts through effectors other than PKB/Akt or Rac and requires at least basal MAP kinase function. Elevated PI 3-kinase activity induces tubulogenesis, but total inhibition and excess activation of the MAP kinase pathway both oppose this effect.