Multicomponent water proton transverse relaxation and T2-discriminated water diffusion in myelinated and nonmyelinated nerve

The influence of compartmental boundaries on water proton transverse relaxation and diffusion measurements was investigated in three distinct excised nerves, namely, the non-myelinated olfactory nerve, the Schwann cell myelinated trigeminal nerve, and the oligodendrocyte myelinated optic nerve of the garfish. The transverse relaxation decay curves were multiexponential and their decomposition yielded three primary components with T2 values approximately 30-50, 150, and 500 ms, which were subsequently assigned to water protons in the myelin, axoplasm, and interaxonal compartments. The short T2 component was absent in the non-myelinated olfactory nerve, but present in both myelinated nerves and thus provides supporting evidence for the use of quantitative T2 measurements to measure the degree of myelination. The signal contribution of each T2 component to the apparent diffusion coefficient measurements was varied by incrementing the spin-echo time with a preparatory CPMG train of radiofrequency pulses. The apparent diffusion coefficient and its anisotropy were shown to be independent of the spin-echo time over the range of 70 to 450 ms.     

Selective activation of JNK1 is necessary for the anti-apoptotic activity of hILP

The balance between the inductive signals and endogenous anti-apoptotic mechanisms determines whether or not programmed cell death occurs. The widely expressed inhibitor of apoptosis gene family includes three closely related mammalian proteins: c-IAP1, c-IAP2, and hILP. The anti-apoptotic properties of these proteins have been linked to caspase inhibition. Here we show that one member of this group, hILP, inhibits interleukin-1beta-converting enzyme-induced apoptosis via a mechanism dependent on the selective activation of c-Jun N-terminal kinase 1. These data demonstrate that apoptosis can be inhibited by an endogenous cellular protein by a mechanism that requires the activation of a single member of the mitogen-activating protein kinase family.     

Measurements of the suitability of large rock salt formations for radio detection of high-energy neutrinos

We have investigated the possibility that large rock salt formations might be suitable as target masses for detection of neutrinos of energies about 10 PeV and above. In neutrino interactions at these energies, the secondary electromagnetic cascade produces a coherent radio pulse well above ambient thermal noise via the Askaryan effect. We describe measurements of radio-frequency attenuation lengths and ambient thermal noise in two salt formations. Measurements in the Waste Isolation Pilot Plant, located in an evaporite salt bed in Carlsbad, NM yielded short attenuation lengths, 3–7 m over 150–300 MHz. However, measurements at United Salt's Hockley mine, located in a salt dome near Houston, Texas yielded attenuation lengths in excess of 250 m at similar frequencies. We have also analyzed early ground-penetrating radar data at Hockley mine and have found additional evidence for attenuation lengths in excess of several hundred meters at 440 MHz. We conclude that salt domes, which may individually contain several hundred cubic kilometer water-equivalent mass, provide attractive sites for next-generation high-energy neutrino detectors.     

Penetration of intravesical doxorubicin in human bladders

The bladder wall penetration kinetics of intravesical doxorubicin were examined in radical cystectomy patients, to provide insight into drug concentrations at target tumor sites. The dosing solution (40 mg/20 ml) was instilled just prior to the start of surgery and maintained for 60-115 min until just prior to bladder excision. The data showed considerable inter-patient variability in the peak plasma concentration (24-fold), urine concentration (7- fold), and tissue concentration (28-fold). The urine concentration at the time of tissue harvest was about 17% of the concentration in the dosing solution. This was due to the dilution by post-catheterization residual urine and urine produced during treatment. The doxorubicin concentration dropped by 32-fold across the urothelium, and declined semi-logarithmically with respect to depth in the capillary-perfused tissues beneath the urothelium with a 50% decrease over about 500 micromole. In three of six patients from whom tumor tissue was obtained, the doxorubicin concentration was higher than the adjacent non-tumor-bearing tissues of comparable tissue depth, whereas the reverse was seen in the remaining three tumors. The plasma concentrations were 0.02, 0.03, 0.05, 0.27, and 0.69% of the concentrations in the tumors, urothelium, lamina propria, superficial and deep muscle layers, respectively. These data indicate: (a) a considerable intra- and inter-patient variability in bladder tissue concentrations, in part due to the variability in the urine concentration; (b) the urothelium is an effective barrier to doxorubicin penetration; and (c) a targeting advantage of intravesical therapy for the treatment of superficial bladder cancer yielding superficial bladder tissue concentrations at least 2000-fold higher than in the systemic circulation. A comparison of the data of doxorubicin with our previously published data on mitomycin C shows similar bladder tissue pharmacokinetics for the two drugs, suggesting that there is no pharmacokinetic preference for either drug.     

Clinical significance of erythrosedimentation rate in cancer in relation to cytokine production: correlation with high IL-6 and low IL-2 blood concentrations

Despite its well documented unfavourable prognostic significance in several human diseases, including cancer, the cytokinic mechanisms responsible for an increased erythrosedimentation rate (ESR) still remain to be better analyzed and defined. The recent possibility to measure cytokine concentrations in the blood of patients has allowed us to explore the possible relation between ESR values and endogenous cytokine secretions. This preliminary study was performed to evaluate the relationship between ESR values and serum levels of IL-2 and IL-6, which represent the most important cytokines responsible for the activation and the suppression, respectively, of host anticancer immune reaction. The study included 33 consecutive solid tumor patients, 22 of whom showed distant organ metastases. Abnormally high values of ESR were present in 21 patients, including 18/22 metastatic patients and 3/11 nonmetastatic patients. Patients with elevated values of ESR showed significantly higher mean levels of IL-6 and significantly lower mean concentrations of IL-2 with respect to those found in patients with normal ESR values. These results would show that cancer-related increase in ESR values is associated with low levels of IL-2 and high levels of IL-6. Since IL-2 plays an essential role in the anticancer immunity and IL-6 may suppress the antitumor immune defenses, the evidence of low levels of IL-2 and high values of IL-6 in cancer patients with increased ESR values would explain the unfavourable prognostic significance of high ESR values in human neoplasms.     

Tyrosine-based membrane protein sorting signals are differentially interpreted by polarized Madin-Darby canine kidney and LLC-PK1 epithelial cells

Tyrosine-dependent sequence motifs are implicated in sorting membrane proteins to the basolateral domain of Madin-Darby canine kidney (MDCK) cells. We find that these motifs are interpreted differentially in various polarized epithelial cell types. The H, K-ATPase beta subunit, which contains a tyrosine-based motif in its cytoplasmic tail, was expressed in MDCK and LLC-PK1 cells. This protein was restricted to the basolateral membrane in MDCK cells, but was localized to the apical membrane in LLC-PK1 cells. Similarly, HA-Y543, a construct in which a tyrosine-based motif was introduced into the cytoplasmic tail of influenza hemagglutinin, was sorted to the basolateral membrane of MDCK cells and retained at the apical membrane of LLC-PK1 cells. A chimera in which the cytoplasmic tail of the H,K-ATPase beta subunit protein was replaced with the analogous region of the Na,K-ATPase beta subunit polypeptide was localized to both surface domains of MDCK cells. Mutation of tyrosine-20 of the H,K-ATPase beta subunit cytoplasmic sequence to an alanine was sufficient to disrupt basolateral localization of this polypeptide. In contrast, these constructs all remain localized to the apical membrane in LLC-PK1 cells. The FcRII-B2 protein bears a di-leucine motif and is found at the basolateral membrane of both MDCK and LLC-PK1 cells. These results demonstrate that polarized epithelia are able to discriminate between different classes of specifically defined membrane protein sorting signals.     

Granzymes D, E, F, and G are regulated through pregnancy and by IL-2 and IL-15 in granulated metrial gland cells

Granulated metrial gland (GMG) cells are NK cells that proliferate and differentiate within the murine uterus during pregnancy. They have been predicted to play important roles in nurturing the embryo, normal placentation, and uterine tissue remodeling. GMG cell differentiation is manifested by the accumulation of the cytolytic mediators, perforin, granzyme A, and granzyme B, within cytoplasmic granules. The signaling mechanisms required for GMG cell differentiation are largely unknown, although recent in vitro assays have implicated IL-15 in these events. In this report, we demonstrate that granzymes D, E, F, and G (granzymes D-G) are also expressed in GMG cells but at a later stage in pregnancy when compared with granzyme A expression. Whereas granzyme A is expressed in early to mid-gestation, the expression of granzymes D-G peak in mid- to late gestation. In addition, we show that the expression patterns of IL-2Rbeta and the IL-2Rgamma mRNAs overlap with that of granzyme D-G mRNAs in the pregnant uterus. Finally, we demonstrate that granzymes D-G are up-regulated by IL-2 and IL-15 in primary cultures containing GMG cells. Taken together, these results suggest that IL-2 and/or IL-15 may regulate GMG cell differentiation in vivo, and that granzymes D-G may have different functions than granzyme A during pregnancy.     

Effect of carbon on the electronic conductivity and discharge capacity LiCoPO4

The effect of added carbon (3, 5 and 10 wt.%) on the electronic conductivity and discharge capacity of LiCoPO₄ was investigated. It was found after heat-treatment that the samples consisted of a LiCoPO₄ majority phase and Co₂P second phase. The added carbon was consumed reducing the LiCoPO₄ surface layers to Co₂P. The electronic conductivity increased as the amount of the Co₂P phase increased. It was observed that the discharge capacity increased with increased Co₂P content to ∼4–5 wt.%, after which the capacity rapidly decreased with increasing Co₂P content. The increase in discharge capacity is likely a result of the increase in electronic conductivity. At higher Co₂P volume fractions the presence of the electrochemically inert Co₂P phase causes decreased capacity by: (1) reducing the amount of LiCoPO₄ present and (2) preventing Li⁺-ions from entering/leaving LiCoPO₄, even though the highest values of electronic conductivity were exhibited.     

Reliability and validity of the Parent-Child Relationship Inventory (PCRI): Evidence from a longitudinal cross-informant investigation.

Psychometric properties of the Parent-Child Relationship Inventory (PCRI) were examined using data collected from adolescents and their parents in the Fullerton Longitudinal Study. Results revealed acceptable internal consistency for most scales and moderate to high 1-year stability for all scales. Both parents' PCRI scores correlated with their views of family climate. Cross-informant concordance was pervasive and strong between mothers' PCRI scores and adolescents' perceptions of the parent-child relationship and family climate; however, convergence was not evident between fathers' and adolescents' reports. Additionally, poor performance was observed for the Autonomy scale. In conjunction with other research on parent-adolescent relationships, concerns are raised regarding the utility of scales to contrast mother-adolescent with father-adolescent relationships. (PsycINFO Database Record (c) 2010 APA, all rights reserved)