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Antibodies were prepared in sheep against purified plasma membranes from pig adipocytes. Western (immuno) blotting revealed reactions of the antisera with a large number of proteins in adipocyte plasma membranes but remarkably few in plasma membranes from muscle, kidney, liver, lung, brain, spleen, and erythrocytes. This illustrated the high degree of specificity the serum had for adipose tissue. When injected into localized subcutaneous sites such antisera were able to cause considerable adipocyte destruction, which resulted in complete loss of adipose tissue from the site for > or = 14 wk. This cell destruction was probably mediated in part by lymphocytic infiltration. Subcutaneous injections were of limited use because of the localized nature of the effects, but, when treatment was administered intraperitoneally, systemic effects were produced that resulted in a 30% reduction in backfat thickness in the region of the last rib and a 25% reduction in fat content of fore- and hind-loin joints that resulted in a significant increase in the percentage of lean tissue. Total feed intake, live weight gain, hot carcass weights, and dressing percentage were unaffected. These results demonstrate the potential for producing long-term reductions in body fat in pigs by an immunization technique that may also provide the unexpected, potential benefit of increased lean deposition. This suggests that fat deposition per se exerts a restrictive influence on lean carcass development.

According to preliminary data, seroconversion after mRNA SARS-CoV-2 vaccination might be unsatisfactory in Kidney Transplant Recipients (KTRs). However, it is unknown if seronegative patients develop at least a cellular response that could offer a certain grade of protection against SARS-CoV-2. To answer this question, we prospectively studied 148 recipients of either kidney (133) or kidney-pancreas (15) grafts with assessment of IgM/IgG spike (S) antibodies and ELISpot against the nucleocapside (N) and the S protein at baseline and 2 weeks after receiving the second dose of the mRNA-1273 (Moderna) vaccine. At baseline, 31 patients (20.9%) had either IgM/IgG or ELISpot positivity and were considered to be SARS-CoV-2-pre-immunized, while 117 (79.1%) patients had no signs of either cellular or humoral response and were considered SARS-CoV-2-naïve. After vaccination, naïve patients who developed either humoral or cellular response were finally 65.0%, of which 29.9% developed either IgG or IgM and 35.0% S-ELISpot positivity. Factors associated with vaccine unresponsiveness were diabetes and treatment with antithymocytes globulins during the last year. Side effects were consistent with that of the pivotal trial and no DSAs developed after vaccination. In conclusion, mRNA-1273 SARS-CoV-2 vaccine elicits either cellular or humoral response in almost two thirds of KTRs.

Myeloid sarcoma (MS) is defined as an extramedullary mass-forming lesion composed of immature myeloid cells. It is a rare but well-known manifestation of acute myeloid leukemia. Pediatrics testicular MS may pose a possible diagnostic challenge, an issue that is underscored in the few testicular pediatric MS cases reported in the literature. Herein, we report a series of 5 cases of pediatric testicular MS that are evaluated at the morphologic and immunohistochemical levels with correlation with the KMT2A (MLL) rearrangement status. Three patients presented with no prior history of acute myeloid leukemia. All 5 cases showed monoblastic morphology; positive for CD33, CD43, CD68, CD163, CD4 (dim), and lysozyme; and negative for CD10, CD34, CD117, and myeloperoxidase. KMT2A (MLL) rearrangement was detected in 4 of the 5 cases. In the literature, 8 more cases of pediatric testicular lymphoma were reported. Most of them showed monocytic differentiation and KMT2A (MLL) rearrangement was reported in 3 of the cases. In conclusions, testicular MS in pediatric patients shows monoblastic differentiation which may be attributed to the KMT2A (MLL) rearrangement. We also highlight the importance of using an extended immunohistochemistry panel in the diagnosis of MS.

The use of S-9 liver fractions to examine metabolism-mediated cytotoxicity in vitro has the inherent problem that not only are activating enzyme systems added, but also deactivation pathways, such as that involving glutathione. The in vivo manipulation of these activating and deactivating systems prior to S-9 preparation is possible with animals, but not with humans. Hence, the possibility of depleting glutathione in target cells and S-9 fractions was evaluated using phorone, a known glutathione-depleting agent. 3T3-L1 mouse fibroblast-like cells and V79 Chinese hamster lung fibroblasts were used as the target cells, and cytotoxicity was assessed by the FRAME (Fund for the Replacement of Animals in Medical Experiments) kenacid blue method. Phorone was found to have a moderate intrinsic cytotoxicity and to effectively deplete cellular glutathione. When phorone was used in the two-component S-9 fraction/target cell system, its toxicity to 3T3-L1 cells was markedly increased, which suggests transformation to a toxic metabolite. The use of S-9 fractions from animals pretreated with phenobarbitone and beta-naphthoflavone resulted in greatly increased phorone toxicity, which indicates the involvement of cytochrome P-450 enzymes in its metabolism. The metabolism-mediated toxicity of phorone was reduced by the addition of exogenous glutathione.

The effectiveness of oral RU 486 and anordrin given alone and in combination for terminating early pregnancy was tested in the rat, rabbit, and hamster. In the rat and rabbit, the combination of RU 486 and anordrin is more effective in terminating pregnancy than either of the two compounds used alone. A non-effective dose of RU 486 combined with a non-effective or a sub-effective dose of anordrin, or a low effective dose of RU 486 in combination with a non-effective dose of anordrin, exerted additive or synergistic effects resulting in resorption of embryos and termination of pregnancy in rats and rabbits. The serum progesterone as well as estradiol concentrations were significantly suppressed by these combinations when pregnancy was terminated. In the hamster, however, RU 486 was not effective in interrupting early pregnancy, even at a 4-fold higher dose than was effective in the rat, due to the fact that RU 486 does not bind to the progestin receptor in this species. Unexpectedly, there were also no effects of anordrin on pregnancy termination in the hamster even at high doses. It is concluded that in rat and rabbit, the synergistic action between RU 486 and anordrin not only greatly enhances efficacy in terminating pregnancy but also reduces substantially the doses required to produce this effect.

Recently, lateral flow assay (LFA) for nucleic acid detection has drawn increasing attention in the point-of-care testing fields. Due to its rapidity, easy implementation, and low equipment requirement, it is well suited for use in rapid diagnosis, food authentication, and environmental monitoring under source-limited conditions. This review will discuss two main research directions of lateral flow nucleic acid tests. The first one is the incorporation of isothermal amplification methods with LFA, which ensures an ultra-high testing sensitivity under non-laboratory conditions. The two most commonly used methodologies will be discussed, namely Loop-mediated Isothermal Amplification (LAMP) and Recombinase Polymerase Amplification (RPA), and some novel methods with special properties will also be introduced. The second research direction is the development of novel labeling materials. It endeavors to increase the sensitivity and quantifiability of LFA testing, where signals can be read and analyzed by portable devices. These methods are compared in terms of limits of detection, detection times, and quantifiabilities. It is anticipated that future research on lateral flow nucleic acid tests will focus on the integration of the whole testing process into a microfluidic system and the combination with molecular diagnostic tools such as clustered regularly interspaced short palindromic repeats to facilitate a rapid and accurate test.

Copper ion (Cu²⁺) plays an important role in the human body because it is beneficial for metabolism. However, an excessive or slight amount of Cu²⁺ can cause various symptoms. Therefore, it is necessary for human health to realize the trace and visual detection of Cu²⁺. Referring to traditional fluorescence test papers, the qualitative and semi-quantitative detection of Cu²⁺ could be realized by a dual-carbon dots (CDs) ratiometric fluorescent paper-based sensor with the advantages of environmental protection, portability and low cost. In this paper, the inkjet-printed test paper with the best mixing ratio of the two CDs has been researched to maximize the spectral energy transfer of ion detection (maximum color gamut expansion). Among them, the preparation method of b-CDs has been improved, increasing the photoluminescence quantum yield (PLQY) to 88.9%. The sensitivity detection limit of the double emission ratio sensor was 0.15 nM in solution, and the human eye can distinguish at least 3 μmol L^-1 Cu²⁺ in the paper-based sensor. Compared with the traditional single-emission sensor, the human eye was more sensitive to the color change of the emission ratio sensor. The results indicate that we not only realized the micro detection of Cu²⁺ with convenient methods, but also provided a promising strategy for the visual detection of Cu²⁺.

Incidence of epilepsy is 0.3 to 0.5% in different populations throughout the world, and the prevalence of epilepsy has been estimated at 5 to 10 persons per 1000. Scanning of the Ayurvedic classics reveals that 90% of the formulations mentioned to have action on sajnavaha srotas are ghrita-based formulations. Ghrita because of its yogavahi guna, incorporates the qualities of the drugs added to it without losing its own qualities. In the present study Hingusauvarchaladi ghrita and saptavartita Hingusauvarchaladi ghrita have been selected, to prove their anticonvulsant activity experimentally on albino mice, by the chemoshock method. The observations recorded have been analyzed by one-way ANOVA followed by Scheffe's test, statistically. Saptavartita Hingusauvarchaladi ghrita has shown better anticonvulsant activity in comparison to Hingusauvarchaladi ghrita.

Posttransplant B-cell lymphoproliferative disorders (PTLDs) constitute a heterogeneous group that includes hyperplastic and unique polymorphic lesions at one end of the spectrum and monomorphic lymphoid proliferations indistinguishable morphologically from conventional B-cell non-Hodgkin lymphomas (NHLs) at the other end. Almost all the PTLDs are of B-cell origin, with only rare examples of T-cell phenotype described. Despite a plethora of information available on the morphologic spectrum, pathogenetic role of Epstein-Barr virus, and various treatment options, a detailed flow cytometric immunophenotypic evaluation of PTLDs is largely lacking.

Pathological vascular remodeling in venous bypass grafts (VGs) results in smooth muscle cell (SMC) intimal hyperplasia and provides the substrate for progressive atherosclerosis, the principal cause of late VG failure. Nitric oxide (NO) bioactivity is reduced in VGs, in association with increased vascular superoxide production, but how these features relate to pathological VG remodeling remains unclear. We used gene transfer of the neuronal isoform of nitric oxide synthase (nNOS) to investigate how increased NO production modulates vascular remodeling in VGs and determined the effects on late VG phenotype.

To investigate the specificity of anti H1 antibodies peptides from the N- and C-domain of H1 and the synthetic oligonucleotide (AT)6 were complexed. Circular dichroism (CD) spectroscopy indicated that the free peptides H1(1-16), H1(204-218) and C(121-210) in low salt buffer assume a random structure but become helical when bound to the oligonucleotide. The structured and unstructured H1 fragments were then analyzed by enzyme linked immunosorbent assay (ELISA) with anti-H1 antibodies in sera from patients with systemic lupus erythematosis (SLE) and with the monoclonal anti-H1 antibody MRA-12 derived from MLR lpr/lpr autoimmune mice. Binding of these antibodies to H1(204-218) and C was inhibited to a level of 50% when these H1 peptides were complexed with (AT)6. When the same antibody was tested with H1 fragment GC(34-210), attachment to oligonucleotide (AT)6 did not influence antibody binding. Competition studies with liquid phase GC and C antigen against solid phase GC and C indicated that liquid phase GC was more efficient in displacing antibody binding reactivity than liquid phase C. The displacement effect of both liquid phase antigens was greatest against solid phase C. We conclude that anti-H1 autoantibodies are directed against an epitope located near the junction of the G- and C-domain which is exposed and not masked when H1 is bound to DNA.

For the first time, using scanning electron microscopy, transmission electron microscopy, X-ray absorption near edge structure and extended X-ray absorption fine structure X-ray diffraction, it is showed that MnCO₃, MnWO₄, Mn₃(PO₄)₂·3H₂O, MnS and Mn(VO₃)₂·xH₂O under the water-oxidation conditions and in the presence of cerium(iv) ammonium nitrate, are converted to Mn oxide without a high-range order. A mechanism is proposed for such conversion and as Mn oxide is an efficient water-oxidizing catalyst, it is thus a candidate as a contributor to the observed catalytic activity.

<b>Objective</b>: The present study investigated the multidimensional nature of the future time perspective scale and dimension-specific associations with measures of physical health, cognitive functioning, and well-being.<b>Method</b>: Using data from the Berlin Aging Study II (<i>N</i>&#8201;=&#8201;1,038, <i>M</i> age = 71&#8201;years, range = 61-88&#8201;years, 52% women), different models of future time perspective were compared using confirmatory factor analyses, and the best-fitting model was then used to explore dimension-specific associations with physical health, cognitive functioning, and well-being measures.<b>Results</b>: A model of future time perspective composed of a <i>focus on opportunities,</i> a <i>focus on life,</i> and a <i>focus on time</i> was found to have the best fit. An extended <i>focus on opportunities</i> was associated with stronger grip strength, more accurate memory, as well as higher life satisfaction and positive affect. An extended <i>focus on time</i> was associated with less accurate memory, lower negative affect, and greater life satisfaction. A <i>focus on life</i> was unrelated to study measures.<b>Discussion</b>: Findings suggest that future time perspective is multidimensional and that these dimensions are differentially associated with physical health, cognitive functioning, and well-being in old age.

We studied tyrosine hydroxylase (TH)-immunoreactive neurons and neuropil in the olfactory bulb of the leopard frog, Rana pipiens, and in the clawed frog, Xenopus laevis. In both frogs, TH processes in the main olfactory bulb showed a trilaminar organization, with a densely stained external glomerular layer (GL), a moderately stained middle mitral cell layer (MCL), and internally a weakly stained internal plexiform layer (IPL) and granule cell layer (GRL). TH-positive cells in the MCL and IPL could be divided into two types. Type 1 cells had one or two thick dendrites that arborized within glomeruli in the GL and often had a thin "axon-like" process that exited the cell on the internal surface, with a recurrent collateral that ascended into the GL. Type 2 cells had beaded dendrites arborizing in the MCL and no discernible axons. Both type 1 and type 2 cells were numerous in the MCL and IPL of Rana, whereas only type 2 cells were common in the MCL and IPL of Xenopus. In the GL, labeled cells were numerous in Xenopus but rare in Rana. Mitral cells were stained retrogradely by tracer injection into the lateral olfactory tract and by local injection into the bulb. In no case was double labeling for TH observed, suggesting that TH-positive cells in frog olfactory bulb are likely to be interneurons. Double labeling with an anti-gamma-aminobutyric acid (GABA) antibody showed that the TH-positive cells formed a population separate from the GABA-containing interneurons.

This study was conducted to investigate whether gastro-protective and gastro-toxic effects of acute and chronic administration of progesterone, estrogen, FSH and LH were related to oxidant and antioxidant parameters. Chronic administration of progesterone at a low dose (1mg/kg), which probably could not stimulate progesterone receptors (PRs), inhibited oxidative stress of FSH in gastric tissue by suppressing FSH. Progesterone (5mg/kg) may have been caused oxidative stress as reflected by PR stimulation. FSH may have decreased antioxidant parameters and increased oxidant parameters via PRs. Chronic administration of low dose of estrogen (1mg/kg) inhibited LH and but could not stimulate alpha-2 adrenergic receptors, which resulted in oxidative stress in gastric tissue. The higher dose of estrogen (5mg/kg), however, could stimulate alpha-2 receptors, exhibited antioxidant activity in acute and chronic administration. While antioxidant activity of estrogen and LH was blocked with yohimbine (an alpha-2 adrenergic receptor blocker), mifepristone prevented the oxidative stress of progesterone and FSH in gastric tissue. It is concluded that low doses of progesterone may inhibit FSH, whereas high doses of estrogen may stimulate alpha-2 receptors, suggesting that LH could have protective and antioxidant hormone effects.

Employing dibenzo-24-crown-8-ether (DB24C8) as a phase-transfer catalyst, monodispersed fluorescent lanthanon-doped magnetic FePt:RE (RE=Eu, Dy, and Ce) nanoparticles about 3 nm in size were synthesized through the reduction of H2PtCl6.6H2O, Fe2(C2O4)3.5H2O, and RE(NO3)3 (RE=Eu, Dy, and Ce) by propylene glycol using oleic acid as the stabilizer in the solvent-thermal system. The conversion of the as-synthesized chemically disordered fcc FePt:RE nanoparticles to a chemically ordered L1 0 structure occurred after annealing treatment at 873 K, and was simultaneously accompanied by a coercivity increase. It is interesting that the amorphous formation trend is strengthened in an europium-doped FePt:Eu alloy accompanied by enhancement of the coercive force. Its thermal stability indicated that the addition of europium can inhibit the phase transformation. Moreover, the optical measurement results proved that FePt:Dy alloy nanoparticles have fluorescent properties.

The synthesis of shape-controlled nanoparticles is currently a hot research topic. However, from an applied point of view, there is still a lack of easy, cheap, and scalable methodologies. In this communication we report, for the first time, the synthesis of cubic platinum nanoparticles with a very high yield using a water-in-oil microemulsion method, which unlike others, such as the colloidal method, fulfills the previous requirements. This shape/surface structure control is determined by the concentration of HCl in the water phase of the microemulsion. The results reported here show that the optimal HCl percentage in the water phase is about 25% to obtain the highest amount of cubic nanostructures. Ammonia electro-oxidation is used as a surface structure sensitive reaction to illustrate HCl surface structure effects. Moreover, in situ electrochemical characterization has been performed to study the nanoparticle surface structure.

For epidermal growth factor receptor mutation-positive (EGFRm) non-small-cell lung cancer (NSCLC), EGFR-tyrosine kinase inhibitors (EGFR-TKIs) are the preferred first-line (1 L) treatment in the advanced setting. Osimertinib, a third-generation EGFR-TKI, received full approval in 2017 for second-line (2 L) treatment of EGFR T790M-positive NSCLC. The REFLECT study characterizes real-world treatment/testing patterns, attrition rates, and outcomes in patients with EGFRm advanced NSCLC treated with 1 L first-/second-generation (1G/2G) EGFR-TKIs before 1 L osimertinib approval.

A total of 44 different phosphines were tested, in combination with [RuCl(2)(C(6)H(6))](2) and three other Ru(II) precursors, for their ability to form active catalysts for the hydrogenation of CO(2) to formic acid. Half (22) of the ligands formed catalysts of significant activity, and only 6 resulted in very high rates of production of formic acid. These were PMe(3), PPhMe(2), dppm, dppe, and cis- and trans-Ph(2)PCH=CHPPh(2). The in situ catalysts prepared from [RuCl(2)(C(6)H(6))](2) and any of these 6 phosphine ligands were found to be at least as efficient as the isolated catalyst RuCl(O(2)CMe)(PMe(3))(4). There was no correlation between the basicity of monophosphines (PR(3)) and the activity of the catalysts formed from them. However, weakly basic diphosphines formed highly active catalysts only if their bite angles were small, while more strongly basic diphosphines had the opposite trend. In situ (31)P NMR spectroscopy showed that trans-Ru(H)(2)(dppm)(2), trans-RuCl(2)(dppm)(2), trans-RuHCl(dppm)(2), cis-Ru(H)(O(2)CH)(dppm)(2), and cis-Ru(O(2)CH)(2)(dppm)(2) are produced as the major metal-containing species in reactions of dppm with [RuCl(2)(C(6)H(6))](2) under catalytic conditions at 50 degrees C.

The role of gram-negative bacteria endotoxin in infectious and non-infectious pathology is reviewed. It is shown that endotoxin may induce some injuries to the lungs, liver, kidney and blood vessels. It is suggested that intestinal microflora endotoxin may take part in the development of many pathological processes. The basis of the endotoxin effect is its capacity to interact with cell membrane. Intravascular blood coagulation and endotoxin shock resulting in the patient's death may occur at high doses of endotoxin.

To characterize further lymphomas which arise in chronically immunosuppressed allotransplant patients, we studied the clinical and histological features of seven cases of nonHodgkin's lymphoma and determined the immunological phenotype in four cases, which developed in a series of 182 patients who underwent cardiac transplantation at Stanford University Hospital. Clinical features which were correlated with the development of lymphoma included patient age, pretransplant diagnosis, and the number of transplants. All cases of nonHodgkin's lymphoma presented as solitary or multiple localized extranodal lesions while none presented in lymph nodes. Extranodal sites of involvement included brain, lung, and soft tissues of the thigh at the site of antilymphocyte serum injections. Histologically, five of seven lymphomas were classified as high grade, large cell, immunoblastic and two of seven as intermediate grade, large noncleaved cell. The immunological phenotype of the neoplasm from four patients was determined by reaction with immunoglobulin light and heavy chain reagents and monoclonal antibodies to T cell and B cell antigens. All lymphomas from four patients which were tested stained for Ia antigen (HLA-DR) but did not stain for immunoglobulin or the T cell antigens detected in this study.

Recently several new direct assay systems for chemical measurement of LDL-cholesterol (Ch) have been developed. These systems allow us to estimate LDL-Ch value even in samples under non-fasting condition as well as samples from prominent hypertriglyceridemics without ultracentrifugation. Since it is possible that the difference between LDL-Ch value measured using new direct method and that calculated using Friedewald's formula can indicate compositional abnormalities of triglyceride-rich lipoprotein (TGRL) fraction (if VLDL-Ch equal to 1/5 of plasma triglyceride, this difference must always be zero), this difference (estimated remnant-Ch) may represent the presence of remnant or intermediate density lipoprotein (IDL) fraction. LDL-Ch is not detected by means of this direct method (LDL-EX, Denka Seiken Co.) in the eluate of the affinity column, which contains anti-apoA1 and anti-B100 antibody, indicating that RLP fraction can be excluded from the assay system. Estimated remnant-Ch correlated well with RLP-Ch, IDL-Ch and apoE. Furthermore, there is no significant correlation between LDL-Ch measured by LDL-EX and Lp(a), indicating that this direct assay system does not include Lp(a) in plasma. Thus, this new direct assay method for LDL-Ch enables us to measure LDL-Ch value with ease and also to estimate compositional abnormalities of TGRL fraction and/or appearance of remnant or IDL fraction without ultracentrifugation.

The complexation of 2-hydroxy-N-(3,4-dimethyl-5-isoxazolyl)-1,4-naphthoquinone-4-imine (I) with a highly soluble cyclodextrin, hydroxypropyl-beta-cyclodextrin (HP-beta-CD) was studied in aqueous media by solubility methods. I is an antibacterial and trypanocidal agent that is undergoing preclinical testing. Unfortunately, I exhibits low water solubility, and it is therefore difficult to prepare the solutions for biological tests. I inclusion took place with 1:1 stoichiometry. The stability constants of the I complexes calculated from the slope and the intercept of the phase solubility diagrams are larger in the less ionized form, whereas greater overall solubility is obtained in basic media.

Specimens of human kidneys (n = 24) were investigated using magnetic resonance imaging (MRI), and compared with the corresponding cross-sections that had been prepared later from the same kidneys. The tomographs reveal detailed informations of renal fine structure. In particular, parenchyma and sinus can be easily differentiated from vasculature. It is possible to visualize vessel arborization, including the arcuate vessels of the renal cortex. The clinical significance of renal MR tomographs is discussed.

The pharmacological basis of perceptual learning and associated cortical reorganizations remains elusive. We induced perceptual learning by Hebbian coactivation of the skin of the tip of the right index finger in humans. Under placebo, tactile two-point discrimination was improved on the coactivated but not on the left index finger. This augmentation was blocked by an N-methyl-D-aspartate-receptor blocker, but doubled by amphetamine. No drug effects were found on the left index finger. The individual amount of cortical reorganization as assessed by mapping of somatosensory evoked potentials was linearly correlated with the pharmacological modulation of discrimination thresholds, implying that perceptual learning and associated cortical changes are controlled by basic mechanisms known to mediate and modulate synaptic plasticity.

A simple method was developed for the generation of cesium iodide (CsI) cluster ions up to m/z over 20,000 in matrix-assisted laser desorption/ionization mass spectrometry (MALDI MS). Calibration ions in both positive and negative ion modes can readily be generated from a single MALDI spot of CsI(3) with 2-[(2E)-3-(4-tert-butylphenyl)-2-methylprop-2-enylidene] malononitrile (DCTB) matrix. The major cluster ion series observed in the positive ion mode is [(CsI)(n)Cs](+), and in the negative ion mode is [(CsI)(n)I](-). In both cluster series, ions spread evenly every 259.81 units. The easy method described here for the production of CsI cluster ions should be useful for MALDI MS calibrations.

Distribution of the sixteen polycyclic aromatic hydrocarbons (PAHs) indicated from USEPA as priority pollutants was studied in surface sediments of two coastal areas of the Adriatic Sea. PAHs were recovered from the sediments by solvent extraction and then analyzed by means of gas chromatography-mass spectrometry. Total concentrations of the analytes in the range 24.1-501.1 ng/g were detected. The observed distribution has been discussed taking into account different aspects, such as the fluvial inputs and the grain size of the sediments. By using a molecular marker approach and characteristic compositional patterns it was possible to ascribe to combustion processes the main source of PAHs. Furthermore a good correlation between benzo[a]pyrene and the total concentration of PAHs (r=0.953) has been pointed out.

Ion conduction in K(+)-channels is usually described in terms of concerted movements of K(+) progressing in a single file through a narrow pore. Permeation is driven by an incoming ion knocking on those ions already inside the protein. A fine-tuned balance between high-affinity binding and electrostatic repulsive forces between permeant ions is needed to achieve efficient conduction. While K(+)-channels are known to be highly selective for K(+) over Na(+), some K(+) channels conduct Na(+) in the absence of K(+). Other ions are known to permeate K(+)-channels with a more moderate preference and unusual conduction features. We describe an extensive computational study on ion conduction in K(+)-channels rendering free energy profiles for the translocation of three different alkali ions and some of their mixtures. The free energy maps for Rb(+) translocation show at atomic level why experimental Rb(+) conductance is slightly lower than that of K(+). In contrast to K(+) or Rb(+), external Na(+) block K(+) currents, and the sites where Na(+) transport is hindered are characterized. Translocation of K(+)/Na(+) mixtures is energetically unfavorable owing to the absence of equally spaced ion-binding sites for Na(+), excluding Na(+) from a channel already loaded with K(+).

BACKGROUND: The aim of this study was to determine in an open trial if physical exercise in sleep apnea patients is safe and/or influences respiratory disturbance index (RDI). METHODS: After being treated 3 months or more with nasal CPAP for moderate to severe sleep apnea syndrome, eleven patients (1 female, 10 male, mean age 52.2 years) began a six-month period of supervised physical exercise twice a week, 2 hours each time. Before and after this period a Polysomnography without CPAP was recorded, along with a bicycle exercise test with lactate profile, echocardiography, body-weight, and body-height measurement. RESULTS: No adverse effects or cardiopulmonary problems were observed. There was no significant change in body weight with physical training; no significant difference in either min SaO2 nor mean SaO2; and no significant improvement in fitness. No adverse cardiopulmonary effects or problems were observed. There was a decrease of the RDI from 32.8 to 23.6 (p < 0.05), without a significant change in the REM-sleep portion of total sleep time (TST), NREM sleep, or TST. CONCLUSIONS: A prescription for mild to moderate exercise is safe in the management of sleep apnea, and, even in the absence of a fitness improvement, there occurred a decrease in RDI without a change in sleep architecture.

Methods are described for the determination of the activity of urea cycle enzymes in human and rat tissues by chromatography and videodensitometry(CV-technique). With specific substrates carbamoyl-phosphate synthetase and ornithine carbamoyltransferase activities were determined as the amounts of citrulline formed. Argininosuccinate synthetase, argininosuccinate lyase and arginase activities were measured from the changes in ornithine concentration. For measuring the activity of five enzymes 5 to 10 mg wet weight of tissue was sufficient. The CV-technique could be conveniently applied for the investigation of enzyme content in samples from human biopsy.

Sex ratios from 62 single-pair matings of normal broodstock O. aureus were highly heterogeneous with an overall deficit of males (41.4%). Peaks in the sex ratio frequency distribution occurred at 1∶1, 3∶5 and 1∶3 (male∶female). Hybridisation of O. aureus with O. mossambicus, O. spilums and O. niloticus produced highly variable sex ratios, suggesting a complexity of hybrid sex determination. Few valid inferences could be made regarding intraspecific sex determination from these hybrid data. Sex ratios from progeny testing of sex-reversed males (1∶3) and most sex-reversed females (1∶0) provide evidence for female heterogamety in O. aureus. Several aberrant ratios observed suggest Mendelian inheritance of an autosomal recessive gene (F,f), epistatic to the major sex-determining gene (W,Z). Sex ratios of triploids and gynogens support the hypothesis of recombination between the centromere and the major sex-determining locus. Progeny testing of a female mitogyne demonstrated the viability of a novel WW "superfemale", which gave only female offspring. Not all data could be explained by a two-factor model of sex determination. Further exceptional sex ratios may be accounted for by rare autosomal or environmental sex-modifying factors. It is concluded that O. aureus has a multifactorial mechanism of sex determination with the underlying primary mechanism of female heterogamety.

Gestational thrombocytopenia (GT) is commonly observed in pregnancies with otherwise limited obstetric and hematologic complications. However, few data are available on the natural history of the disease, and on the recurrence of thrombocytopenia in subsequent pregnancies. From June 1987 to December 1993, 37 consecutive patients with GT were enrolled in a prospective study, with a total of 41 pregnancies observed. Vaginal delivery was carried out in 33/41 (80%); two patients were transfused fused with packed red cells for obstetric hemorrhage (post-partum uterine atony). Neonatal bleeding did not occur. In all newborns platelet count was performed within 24 hours after delivery: 2 newborns had mild (80 and 75 x 10(9)/L) and 1 severe thrombocytopenia (12 x 10(9)/L) at birth; all of them recovered to a normal platelet count within 10 days without treatment. Twenty-eight out of 3% patients were followed for 12 months after delivery; in 23 a normalization of platelet count occurred within 1-5 months from delivery; in 5 mild thrombocytopenia (100-120 x 10(9)/L) persisted during follow-up. Four patients had a second pregnancy and recurrence of thrombocytopenia was observed in all of them. GT is rarely associated with bleeding episodes during pregnancy and partum, and recovers spontaneously within few months after delivery but thrombocytopenia can recur in subsequent pregnancies. Severe thrombocytopenia is not observed in newborns so that a conservative management is warranted.

There is evidence to suggest that an association exists between oral infections and coronary heart disease (CHD). Subjects presenting lesions of endodontic origin (LEOs) or pulpal inflammation had an increased risk of developing CHD. However, findings concerning systemic manifestations of apical periodontitis (AP) remain controversial. An association between CD14 gene polymorphisms and atherosclerosis-associated diseases has been shown, but there are no data regarding an association between CD14 polymorphism and AP. This study evaluated associations between clinical oral health status, CD14 polymorphisms, and CHD.

The aim of this work was to apply flow cytometry in order to assess and compare the viability of freeze-dried entrapped bacteria with an usual technique by quantification by plate count techniques. It also aimed at studying the effect of various cryoprotectants on the viability of an entrapped Bifidobacterium bifidum subjected to freeze-drying to check their ability to be delivered all along the gastro-intestinal tract. The alginate-pectinate beads were chosen as the encapsulation matrix added with different protectants. The beads were characterized by scanning electron microscopy and the viability was checked by both methods. The best combination to improve viability of entrapped bacteria subjected to freeze-drying is made of glycerol 20% (one cryoprotectant) and sodium ascorbate 10% (one anti-oxidative compound). This study also demonstrates that flow cytometry allows assessment of entrapped bacteria viability. Indeed we showed that viability evaluated by plate method is correlated to that obtained by flow cytometry. So, flow cytometry is a rapid method to determine cell viability after encapsulation and freeze-drying. Finally, these beads seem to be a promising probiotic delivery system to target the colon.

The literature on medical student career choice has identified several influences that can be categorized as student demographics, medical school characteristics, students' perceptions of specialty characteristics, and student-held values. A logistic regression model that included demographics, medical school, and student-rated influences as a proxy for perceptions and values was used to determine their relative contribution to student career choice for three consecutive cohorts of senior medical students attending two schools (n = 649). This model identified a positive relation between choice of primary care career and both student-rated influences and one student demographic characteristic, but not between career choice and school attended. Variables positively correlated with primary care career choice were related to working with people and marital status. Negatively correlated variables were related to income and prestige.

Indoleamine 2,3-dioxygenase (IDO) is a heme dioxygenase which has been shown to be involved in the pathological immune escape of diseases such as cancer. The synthesis and structure-activity relationships (SAR) of a novel series of IDO inhibitors based on the indol-2-yl ethanone scaffold is described. In vitro and in vivo biological activities have been evaluated, leading to compounds with IC(50) values in the micromolar range in both tests. Introduction of small substituents in the 5- and 6-positions of the indole ring, indole N-methylation and variations of the aromatic side chain are all well tolerated. An iron coordinating group on the linker is a prerequisite for biological activity, thus corroborating the virtual screening results.

Quantitative markers extracted from resting-state electroencephalogram (EEG) reveal subtle neurophysiological dynamics which may provide useful information to support the diagnosis of seizure disorders. We performed a systematic review to summarize evidence on markers extracted from interictal, visually normal resting-state EEG in adults with idiopathic epilepsy or psychogenic nonepileptic seizures (PNES). Studies were selected from 5 databases and evaluated using the Quality Assessment of Diagnostic Accuracy Studies-2. 26 studies were identified, 19 focusing on people with epilepsy, 6 on people with PNES, and one comparing epilepsy and PNES directly. Results suggest that oscillations along the theta frequency (4-8 Hz) may have a relevant role in idiopathic epilepsy, whereas in PNES there was no evident trend. However, studies were subject to a number of methodological limitations potentially introducing bias. There was often a lack of appropriate reporting and high heterogeneity. Results were not appropriate for quantitative synthesis. We identify and discuss the challenges that must be addressed for valid resting-state EEG markers of epilepsy and PNES to be developed.

The kidney is a vital organ and susceptible to various diseases. Photoacoustic (PA) imaging provides a powerful technique for studying kidney dysfunction, for which many smart photoacoustic imaging agents have been developed. But the complete clearance of the introduced contrast agents after imaging remains to be challenging, leading to long-term toxicity concerns. In this study, we synthesized black phosphorous quantum dots (BPQDs) with ultra-small size (1.74 ± 0.23 nm after surface modification) and strong PA signal for imaging kidney dysfunction. Importantly, the renal-clearance property and biodegradability of the developed BPQDs help circumvent the long-term toxicity issue for in vivo studies. Based on these BPQDs, both acute kidney injury and chronic kidney disease were successfully detected in the living mice by PA imaging, with higher detection sensitivity than the clinical serum indices examination method. This BPQDs-based PA imaging method should have a promising potential for the early diagnosis of kidney dysfunction in clinic.

During the late nineteenth and early twentieth centuries, toothache must have been a common complaint in Ireland, to judge from the number of toothache 'cures' reported as part of The Schools' Collection (SC) or 'Bailiúchán na Scol', a folklore-collecting scheme that was undertaken in the Irish Republic in 1937 and 1938, and upon which this article is based. These cures range from quasi-medical treatments, such as packing the affected tooth with tobacco, to more folkloric, or magico-religious cures, such as licking a frog or pulling out a tooth from a corpse, as well as herbal and mineral remedies.

Enophthalmos previously has been reported to be a rare complication of maxillary sinus mucoceles. We report three patients treated by the senior author (T.C.C.) over a 2-month period for enophthalmos or obvious deformity of the midface associated with complete opacification of the maxillary antrum. Most previous authors have stressed the role of chronic pressure necrosis or osteitis leading to bone destruction, with primary involvement of the orbital floor. No patients in this series had symptoms typical of maxillary sinus mucoceles. Two of our three patients presented with minimal symptoms of chronic infection. There was inward collapse of the anterior, superior, lateral, and medial walls of the maxillary sinus, with no radiographic or intraoperative confirmation of bone destruction. We speculate that this process may be the result of chronic maxillary hypoventilation with subsequent atelectasis of the antrum secondary to chronic negative pressure. All patients had obstruction at the osteomeatal complex and were treated by endoscopic enlargement of the natural maxillary ostium.

Cancer cells developing multidrug resistance (MDR) is one of the most serious clinical problems responsible for the failure of cancer chemotherapy. P-glycoprotein (P-gp) overexpression and inhibitor of apoptosis proteins (IAPs) overexpression in cancer cells are the two common mechanisms of MDR. However, the relationship between IAPs and P-gp in MDR cancer cells is unknown. We investigated the expression levels of two IAPs, Survivin and XIAP, and their interaction with P-gp in MDR cancer cells. We have found that the human epidermoid carcinoma cells KBv200 and breast cancer cells MCF-7/Adr overexpress not only P-gp but also XIAP and Survivin, and showed high resistance to chemotherapeutic drugs doxorubicin, docetaxel and vincristine, in contrast to their parental cells KB and MCF-7. Furthermore, upregulation of Survivin or XIAP through transfection with the plasmid pECFPN1-Survivin or pcDNA3-6myc-XIAP in these four cell sublines did not affect the P-gp expression. Downregulation of Survivin or XIAP through transfection with the Survivin or XIAP siRNA did not have an effect on the P-gp expression in these resistant cells. Additionally, our immunoprecipitation results showed that Survivin or XIAP did not directly bind to P-gp. In summary, our study suggested that the overexpression of Survivin and XIAP in MDR cancer cells does not directly interact with P-gp.

A simple and efficient synthesis of novel estrone 16&#945;,17&#945;-oxazoline derivatives substituted at the D ring (compounds 6a-g) is described. The reduction of 16&#945;-azido-3-methoxyestra-1,3,5-trien-17-one (1) in methanol in the presence of CeCl₃ under the condition of the Luche reaction produced two epimeric azido alcohol (16&#945;-azido-17&#945;-hydroxy and 16&#945;-azido-17&#946;-hydroxy) derivatives of estra-1,3,5(10)-triene-3-methyl ether (compounds 2 and 3) in a yield of 90% and 7.6%. The reaction of the sterically unhindered 16&#945;-azido-17&#945;-hydroxy-estra-1,3,5(10)-triene-3-methyl ether (2) with a range of benzaldehydes under the condition of the Schmidt rearrangement yielded d-ring substituted estrone 16&#945;,17&#945;-oxazoline derivatives 6a-g. The in vitro antiproliferative activities of compounds 1, 2, 3, 6a-g were also determined by means of MTT assays on a panel of human cancer cell lines HeLa, SiHa, C-33 A, A2780, MCF-7, MDA-MB-231 and T47D.

To determine the normal values of P wave duration and P dispersion (Pd=maximum P wave duration-minimum P wave duration) in healthy children, electrocardiograms of 232 healthy children (143 boys, 89 girls, aged 7 to 15 years) were examined. There was no significant gender difference in maximum P wave duration (103+/-9.5 msec vs 102+/-8.4 msec, p=0.23) or P dispersion (27.2+/-5.3 msec vs 26.8+/-6.2 msec, p=0.643). Maximum P wave duration (r=0.23, p<0.01) and P dispersion (r=0.16, p<0.01) were related to age. We conclude that age affects the P wave duration and P dispersion in healthy children, and thus, should be taken into account when maximum P wave duration and P dispersion are considered for any purpose in healthy children.

In the present study, rapid resolution liquid chromatography was coupled with quadrupole time-of-flight tandem mass spectrometry (RRLC-Q-TOF-MS) to identify the absorbed components and metabolites in rat urine after oral administration of Buyang Huanwu decoction (BYHWD). After oral administration of BYHWD, urine samples were collected and pretreated by solid phase extraction. The mass measurements were accurate within 5 ppm of error for all the protonated molecules, and subsequent fragment ions offered higher quality structural information for interpretation of the fragmentation pathways of various compounds. A total of 50 compounds were detected in rat urine samples within 20 min, including 12 parent compounds and 38 metabolites. Except for three prototype components (Hydroxysafflor yellow A, Paeoniflorin, and Amygdalin), the metabolites identified mainly came from Radix Astragali, Radix Angelicae Sinensis, and Rhizoma Chuanxiong. The results indicated that glucuronidation and sulfation were the major metabolic pathways of isoflavonoids, while glutathione conjugation, glucuronidation and sulfation were the main metabolic pathways of phthalides. No saponin-related metabolites were detected. The present study provided important structural information on the metabolism of BYHWD. Furthermore, the results of this work have demonstrated the feasibility of the RRLC/ESI-Q-TOF-MS approach for rapid and reliable characterization of metabolites from herbal medicines.

Expression of class II antigens on human intestinal epithelial cells was assessed using a sensitive avidinbiotin-peroxidase technique. HLA-DR was present predominantly in the normal small bowel with diminished but evident expression in the colon. HLA-DP staining was less prominent, and HLA-DQ was absent. In inflammatory bowel disease the expression of both HLA-DR and HLA-DP was increased, but that for HLA-DQ remained absent, suggesting an inherent defect in the ability of intestinal epithelial cells to express HLA-DQ. In related experiments, an interferon gamma-treated malignant epithelial cell line T84 also failed to stain for HLA-DQ and HLA-DP despite the presence of HLA-DR. Isolated RNAs for all three subclasses of HLA-D were detectable by slot-blot analysis, suggesting that the lack of HLA-DQ expression relates to posttranscriptional defects in intestinal epithelium. These and other differences with conventional class II antigen-positive accessory cells (macrophages/B cells) may help to explain the unique properties of intestinal epithelial cells as antigen-presenting cells.

By 120 schizophrenic patients of the out-patient clinic or the social Psychiatric Service in Zurich, all mental hospital treatments were recorded (dates of admission and discharge). 65 patients, who became ill before 1973, were compared with 55, who first became ill after 1973. The frequency and duration of the hospitalisations were examined. Three variations were employed in the statistical comparisons, regarding: age groups (generations), time periods and a combination of both. None of these three variations showed any significant difference in frequency or duration of hospitalisation. During the first 4 1/2 years of illness, both generations were similarly frequent and long in hospital, namely, on the average, 3 months per year and once every 12 to 15 months.

Cultured confluent human umbilical vein endothelial cells were irradiated in vitro with 60Co gamma rays at doses from 0 to 50 Gy. After irradiation thrombomodulin was measured at different times over 6 days in the supernatants of endothelial cell culture medium, on the surface of the cells, and within the cells. At 24 h after irradiation, an increase in the release of thrombomodulin from irradiated endothelial cells and an increase in the number of molecules and the activity of thrombomodulin on the surface of the cells were observed; these reactions were dependent on radiation dose. The capacity of the cells to produce and release thrombomodulin was decreased from 2 to 6 days after exposure to 60Co gamma rays. Our data indicate that radiation can injure endothelial cells, and that thrombomodulin may be used as a marker of radiation-induced injury in endothelial cells. The interrelationship between the dysfunction of irradiated endothelial cells and the pathological mechanisms of acute radiation disease is also discussed.

Food production has increasingly become effective but not necessarily sustainable. Transitioning toward circular production systems aiming to minimize waste and reuse materials is one of the means to obtain a more sustainable food production system. However, such a circular food production system can also lead to the accumulation and recirculation of chemical hazards. A literature review was performed to identify potential chemical hazards related to the use of edible and non-edible resources in agriculture and horticulture, and edible plant and animal by-products in feed production. The review revealed that limited information was available on the chemical hazards that could occur when reusing crop residues in circular agriculture. Frequently mentioned hazards present in edible and non-edible resources are heavy metals, process and environmental contaminants, pesticides and pharmaceuticals. For feed, natural toxins and pharmaceutical residues are of potential concern. Studies, furthermore, indicated that plants are capable of taking up chemical hazards when grown on contaminated soil. The presence of chemical hazards in manure, sewage sludge, crop residues, and animal by-products may lead to accumulation in a circular food production system. Therefore, it is relevant to identify these hazards prior to application in food production and, if needed, take precautionary measures to prevent food safety risks.

A 41-years-old man with ileitis terminalis was presented. He was operated on for chronic abdominal pain, and the histological investigation revealed the Crohn's disease. From among the extraintestinal complications the rare muscle involvement joined the inflammatory bowel disease. The leading symptoms were the progressive muscle pain and tenderness presented early before the verification of intestinal problems. His complaints referred mainly to the calf muscles. The electromyography (EMG) was normal, the serum creatinine-kinase (CK) activity has not increased. The most characteristic histological findings were the slight mononuclear cell infiltrations with large histiocytic cells in the perimysial connective tissue. Occasionally the infiltrations were more prominent resembling granuloma formations. The oxidative enzyme reactions and the electron micrographs showed mild mitochondrial changes. Neither non-steroid antiinflammatory nor steroid medication subsided the complaints.

Counts of the number of bacteria in canine urine samples have a bimodal distribution similar to that found in man. Therefore it is reasonable to accept the same criterion of significant bacteriuria in the dog as in man, namely a count of 10(5) or more organisms/ml. of urine. The incidence of significant bacteriuria in the total canine population was 1.4%. It was higher in bitches compared with male dogs, and higher in older animals. The larger proportion of Boxers affected was attributed to their greater age compared with the mean of the sample population. The most frequently observed clinical signs in case of significant bacteriuria were haematuria, incontinence and frequent urination, and only 4.1% of such cases were asymptomatic.

Conductive polymer composite sensors have shown great potential in identifying gaseous analytes. To more thoroughly understand the physical and chemical mechanisms of this type of sensor, a mathematical model was developed by combining two sub-models: a conductivity model and a thermodynamic model, which gives a relationship between the vapor concentration of analyte(s) and the change of the sensor signals. In this work, 64 chemiresistors representing eight different carbon concentrations (8-60 vol% carbon) were constructed by depositing thin films of a carbon-black/polyisobutylene composite onto concentric spiral platinum electrodes on a silicon chip. The responses of the sensors were measured in dry air and at various vapor pressures of toluene and trichloroethylene. Three parameters in the conductivity model were determined by fitting the experimental data. It was shown that by applying this model, the sensor responses can be adequately predicted for given vapor pressures; furthermore the analyte vapor concentrations can be estimated based on the sensor responses. This model will guide the improvement of the design and fabrication of conductive polymer composite sensors for detecting and identifying mixtures of organic vapors.

This article reports results of a field test of work capacity on 30 male farmers ranging in age from 15-54. It involved a self-paced walk from the valley floor, up the mountain wall, and return, with heart rate monitoring. The route was 2.21 km long with a vertical rise of about 200 m. At its steepest, the grade was about 34 degrees, requiring long runs of steps cut into the mountain face. The purpose of this research was to determine whether biological and behavioral traits of individual men help to explain household economic productivity to which they contribute. The traits included anthropometry and a new measure of self-paced, voluntary work capacity (heart rate x time). Income per productive adult increased as did the relative fitness index (heart rate increase above resting x min taken to finish the course). However, the number of rice bundles earned per family, expected to increase with more fit workers, increased with the number of household adults and sitting height (adjusted R(2) = 0.392), but not with self-paced fitness markers. Am. J. Hum. Biol. 12:192-200, 2000. Copyright 2000 Wiley-Liss, Inc.

We assessed the capacity of four probiotic bacteria (Lactobacillus acidophilus, Lactobacillus reuteri, Lactobacillus casei GG, and Bifidobacterium animalis) to colonize, infect, stimulate immune responses in, and affect the growth and survival of congenitally immunodeficient gnotobiotic beige-athymic (bg/bg-nu/nu) and beige-euthymic (bg/bg-nu/+) mice. The bacteria colonized and persisted, in pure culture, in the alimentary tracts of both mouse strains for the entire study period (12 weeks). Although all adult and neonatal beige-euthymic mice survived probiotic colonization, some infant mortality occurred in beige-athymic pups born to mothers colonized with pure cultures of L. reuteri or L. casei GG. The probiotic bacteria manifested different capacities to adhere to epithelial surfaces, disseminate to internal organs, affect the body weight of adult mice and the growth of neonatal mice, and stimulate immune responses. Although the probiotic species were innocuous for adults, these results suggest that caution and further studies to assess the safety of probiotic bacteria for immunodeficient hosts, especially neonates, are required.

This review critically evaluates a broad range of literature in order to show the relationship between meibum, tear lipids and the tear film lipid layer (TFLL). The relationship of meibum composition to dry eye syndrome is briefly discussed. The review also explores the interactions between aqueous and the TFLL by examining the correlations between meibomian lipids and lipids extracted from whole tears, and by considering protein adsorption to the TFLL from the aqueous. Although it is clear to the authors that a normal tear film resists evaporation, an emerging idea from the literature is that the main purpose of the TFLL is to allow the spread of the tear film and to prevent its collapse onto the ocular surface, rather than to be an evaporative blanket. Current models on the possible structure of the TFLL are also examined.

Aspergillus peritonitis is a rare disease in continuous peritoneal dialysis. It is a severe form of peritonitis, which is frequently lethal. We report a case of Aspergillus fumigatus peritonitis in a female patient on automated peritoneal dialysis (APD), who was successfully treated with intravenous amphotericin B and the removal of the peritoneal catheter. As delayed treatment has an increased mortality rate, it is mandatory to remove the catheter and to start intravenous treatment with amphotericin B empirically.

A procedure was developed for estimation of galactocerebroside beta-D-galactosidase activity in leukocytes using a new fluorogenic compound 6-hexadecanoylamino-4-methylum-belliferyl-beta-D-galactop yra noside (HMGal) as a substrate. Some patterns of the fluorometric procedure were compared with corresponding parameters of the spectrophotometric method in which a chromogenic substrate HNGal was used. Sensitivity of the fluorometric procedure with HMGal as a substrate was increased 100-fold as compared with the spectrophotometric method. At the same time, the fluorometric procedure enabled to reduce considerably the incubation period and the cell protein content per an assay. High sensitivity and reproducibility of the procedure with HMGal as a substrate allowed to carry out biochemical diagnosis of Krabbe disease in leukocytes.

A microcolony assay was used in conjunction with fractionated gamma irradiation to determine the number of clonogens in murine intestinal crypts with varying doses of irradiation used in the determination. The experimental design allows direct comparison between two-dose methodologies, employing one and two (or two or four) equal dose fractions, and multiple-dose methodologies involving determination of the crypt survival curves for a number of fractionation regimens using equal doses per fraction. The two-dose methodology yielded estimates of clonogen number of between 3 and 4 at low delivered dose (single and double fractions each of 6.5-7.5 Gy), rising to around 40 at high biological doses (two and four fractions each of 5.75 or 6.5 Gy). The multifraction methodology yielded estimates of clonogen number which increased from 13 after a single fraction to values of 26 and 22 after three and four fractions. However, the latter values were reduced to 11 and 9, and showed little evidence of any dependence on fraction number, when data pertaining to high biologically effective doses were excluded. Hence it is concluded that the high values for clonogen number typically deduced from such multiple-dose protocols, compared with the generally lower (but dose-dependent) values obtained from two-dose protocols, may be explained at least partially by the higher biological doses generally employed in the multiple-dose protocols.

Transcription of mRNAs culminates in RNA cleavage and a coordinated polyadenylation event at the 3' end. In its journey to be translated, the resulting transcript is under constant regulation by cap-binding proteins, miRNAs, and RNA binding proteins, including poly(A) binding proteins (PABPs). The interplay between all these factors determines whether nuclear or cytoplasmic exoribonucleases will gain access to and remove the poly(A) tail, which is so critical to the stability and translation capacity of the mRNA. In this chapter, we present an overview of two of the key features of the mRNA life-cycle: cleavage/polyadenylation and deadenylation, and describe biochemical assays that have been generated to study the activity of each of these enzymatic reactions. Finally, we also provide protocols to investigate mRNA's poly(A) length. The importance of these assays is highlighted by the dynamic and essential role the poly(A) tail length plays in controlling gene expression.

The present study was undertaken to evaluate the potential cancer chemopreventive effects of novel synthetic derivatives of isoflavones. Initially these agents were tested in a mouse mammary organ culture (MMOC) model. Phenoxodiol (2H-1-benzopyran-7-O1,3-(4-hydroxyphenyl)), the most effective in this assay, was selected for further testing in female Sprague-Dawley rats. The agent was tested at 0 (basal diet), 50 and 75 mg/kg diet. Mammary carcinomas in these three groups were induced by dimethylbenz[a]anthracene (DMBA) injected 1 week after the animals started eating the experimental diets. Phenoxodiol significantly reduced tumour incidence rate at both doses (P<or=0.05). Tumour latency was increased from 70.4 days in the control group to 92.9 (P=0.04) days and 97.8 (P=0.03) days in the groups that were fed 50 and 75 mg/kg phenoxodiol, respectively. Compared with the control that was fed basal diet, tumour multiplicity was reduced by 42% (P=0.04) in the group that was fed 50 mg/kg phenoxodiol and by 49% (P=0.01) in the group that was fed 75 mg/kg phenoxodiol. Two additional groups that were not exposed to DMBA, one fed the basal diet and the other a diet containing 75 mg/kg phenoxodiol, were free of tumours. These data suggest that phenoxodiol is an effective chemopreventive agent against DMBA-induced mammary carcinogenesis.

In this study, curved nanostructures, which are difficult to obtain, were created on an Si substrate through the bonding, swelling, and breaking processes of the polymer and silicone substrate. This method can be utilized to obtain convex nanostructures over large areas. The method is simpler than typical semiconductor processing with photolithography or compared to wet- or vacuum-based dry etching processes. The polymer bonding, swelling (or no swelling), and breaking processes that are performed in this process were theoretically analyzed through a numerical analysis of permeability and modeling. Through this process, we designed a convex nanostructure that can be produced experimentally in an accurate manner.

To determine the specificity of neuroendocrine protein gene product (PGP9.5) gene transcripts for detecting micrometastatic neuroblastoma, we have used a highly sensitive polymerase chain reaction (PCR) technique to evaluate expression of this gene in normal blood and bone marrow. While expression of the tyrosine hydroxylase gene was not detected in any normal sample, low-level PGP9.5 expression was detected in eight out of ten blood and seven of 12 marrow samples. PGP9.5 gene transcripts in normal tissues have the potential to interfere with the detection of micrometastatic neuroblastoma.

Phloem, a specialized plant tissue, serves as a superhighway for macromolecular exchanges between different organs or tissues in plants. These mobile macromolecules may function as signaling molecules to sense intrinsic developmental cues or environmental inputs. Among these mobile molecules, RNAs generally need non-cell-autonomous pathway proteins (NCAPPs) to bind to and help them move along the symplasmic passage (through plasmodesmata) into the phloem stream. Grafting experiments combined with next-generation sequencing discovered that around 11.4% of identified Arabidopsis mobile mRNAs have a tRNA-like structure (TLS) motif. Adding an artificial tRNA-like structure at the 5' end of cell-autonomous RNAs (e.g., GUS transcript) can trigger its mobility and movement across a grafting junction to distant organs. Based on the accumulated data and the role of the TLS motif in RNA mobility, we built a web server in our database PLaMoM (a database for plant mobile macromolecules) to enable plant biologists to predict and analyze the transcripts they are interested in. In this chapter, we describe how to use our built-in web server to investigate RNA mobility.

Electromyography (EMG) signals are commonly recorded using the Ag/AgCl gel electrodes in myoelectric prosthetic control. While a gelled electrode may provide high-quality EMG recordings, it is inconvenient in clinical application of a myoelectric prosthesis. A novel type of signal sensors-textile electrodes should be ideal in control of myoelectric prostheses. However, it is unknown whether the performance of textile electrodes is comparable to commonly used electrodes in classifying arm movements. In this study, the custom-made bipolar textile electrodes were fabricated using copper-based nickel-plated conductive fabric and were used to record EMG signals. The performance of EMG signals recorded with textile electrodes in identifying nine arm and hand movements were investigated. Our pilot results showed that the average classification accuracy across six able-bodied subjects was 94.05% when using textile electrodes and 94.26% when using conventional electrodes, with no significant difference between the two types of electrodes (p=0.81). The pilot results suggest that the textile electrodes could achieve similar performance in classifying arm movements in control of myoelectric prostheses as the gelled metal electrodes.

Four methods for calculating gentamicin sulfate dosage requirements were evaluated in 96 patients and compared with an individualized method. The pharmacokinetic parameters of gentamicin were determined from serum concentration time data and used to calculate individualized dosage regimens. Doses were determined in each patient using the "predictive methods" (Sarubbi-Hull, Dettli, "rule of eights," and Chan). Resultant serum concentrations were calculated from doses arrived at by each method. These dosing methods resulted in a large proportion of patients with subtherapeutic or potentially toxic concentrations, or both. The Dettli and Chan methods produced therapeutic concentrations in more patients than the Sarubbi-Hull and rule of eights methods. Desired therapeutic concentrations were attained in significantly more patients with the individualized method than with the predictive methods, and, in addition, larger doses were required. The use of predictive dosage methods should be followed with serum concentration determinations and dosage adjustment to ensure therapeutic concentrations early in treatment.

A novel nonconjugative plasmid of 28,489 bp from a porcine linezolid-resistant Enterococcus faecium isolate was completely sequenced. This plasmid harbored a novel type of multiresistance gene cluster that comprised the resistance genes lnu(B), lsa(E), spw, aadE, aphA3, and two copies of erm(B), which account for resistance to macrolides, lincosamides, streptogramins, pleuromutilins, streptomycin, spectinomycin, and kanamycin/neomycin. Structural comparisons suggested that this plasmid might have developed from other enterococcal plasmids by insertion element (IS)-mediated interplasmid recombination processes.

Even though classical Hodgkin lymphoma is highly curable, the outcome of patients with a refractory or relapsed disease has been disappointing. Multiple lines of therapy are available for patients after their first failure, and most respond to subsequent therapies. However, there is a sizable proportion that remains relapsing/recurrent even after several lines of therapy. The overall prognosis of patients with relapsing and recurrent classical Hodgkin lymphoma (rrcHL) has been very disappointing until recently. Immune checkpoint inhibitors such as the anti-programmed death 1 (PD-1) receptor antibodies have recently been approved to treat relapsed and refractory cHL and have significantly improved the outcome of patients with rrcHL. The approved immune checkpoint inhibitors for relapsed and refractory cHL are nivolumab and pembrolizumab. In the Checkmate 205 study nivolumab demonstrated an objective response rate of 69% with an acceptable safety profile. Similarly, pembrolizumab demonstrated an overall response rate (ORR) of 69% with a complete remission rate (CRR) of 22.4% in the KEYNOTE-087 study in heavily pretreated patients with rrcHL.

Sterile inflammation is a central element in liver diseases. The immune response following injurious stimuli involves hepatic infiltration of neutrophils and monocytes. Neutrophils are major effectors of liver inflammation, rapidly recruited to sites of inflammation, and can augment the recruitment of other leukocytes. The NLRP3 inflammasome has been increasingly implicated in severe liver inflammation, fibrosis, and cell death. In this study, the role of NLRP3 activation in neutrophils during liver inflammation and fibrosis was investigated. Mouse models with neutrophil-specific expression of mutant NLRP3 were developed. Mutant mice develop severe liver inflammation and lethal autoinflammation phenocopying mice with a systemic expression of mutant NLRP3. NLRP3 activation in neutrophils leads to a pro-inflammatory cytokine and chemokine profile in the liver, infiltration by neutrophils and macrophages, and an increase in cell death. Furthermore, mutant mice develop liver fibrosis associated with increased expression of pro-fibrogenic genes. Taken together, the present work demonstrates how neutrophils, driven by the NLRP3 inflammasome, coordinate other inflammatory myeloid cells in the liver, and propagate the inflammatory response in the context of inflammation-driven fibrosis.

The action potential duration (APD) of histamine-induced slow action potentials (SAP) and force of contraction (FC) were potentiated by nicotine (0.6-1.0 mmol.L-1) on guinea pig papillary muscles in a concentration-dependent manner. In the presence of atropine, nicotine concentration dependently suppressed the action potential amplitude (APA), APD, the maximal upstroke velocity (Vmax), and FC in catecholamine-depleted (reserpine 2.5 mg.kg-1 ip, 15 h prior to the experiment) muscles. Nicotine (0.6 mmol.L-1) itself induced SAP and enhanced FC. These 2 effects were antagonized by verapamil. A linear relationship existed between APA of nicotine-induced SAP and 1g [Ca2+]0 with a slope of 23.2 mV for a 10-fold change in [Ca2+]0. These results suggested that the effects of nicotine on enhancing Isi were mediated by the release of catecholamines in myocardium.

Since ancient times the Mediterranean island of Sardinia has been known for harboring a population with an average body height shorter than almost every other ethnic group in Europe. After over a century of investigations, the cause(s) at the origin of this uniqueness are not yet clear. The shorter stature of Sardinians appears to have been documented since prehistoric times, as revealed by the analysis of skeletal remains discovered in archaeological sites on the island. Recently, a number of genetic, hormonal, environmental, infective and nutritional factors have been put forward to explain this unique anthropometric feature, which persisted for a long time, even when environmental and living conditions improved around 1960. Although some of the putative factors are supported by sound empirical evidence, weaker support is available for others. The recent advent of whole genome analysis techniques shed new light on specific variants at the origin of this short stature. However, the marked geographical variability of stature across time and space within the island, and the well-known presence of pockets of short height in the population of the southern districts, are still puzzling findings that have attracted the interest of anthropologists and geneticists. The purpose of this review is to focus on the state-of-the-art research on stature, as well as the factors that made Sardinians the shortest among Europeans.

Functional high-affinity interleukin-2 receptors (IL-2R) contain three transmembrane proteins, IL-2R alpha, beta and gamma. We have investigated the expression of IL-2R alpha and beta genes in immature mouse thymocytes. Previous work has shown that during differentiation these cells transiently express IL-2R alpha on their surface. Stimulation of IL-2R alpha+ and IL-2R alpha- immature thymocytes with phorbol 12-myristate 13-acetate and calcium ionophore induces synthesis of IL-2R alpha and IL-2R beta mRNA. Most of this response depends on autocrine stimulation by IL-2. IL-1 synergizes with IL-2 to induce a 120-fold increase in IL-2R alpha mRNA and a 14-fold increase in IL-2R beta mRNA levels. A large proportion of the stimulated cells contains both transcripts. These interleukins do not induce any differentiation to more mature phenotypes. Collectively, these results show that IL-2 plays a major role in the regulation of IL-2R expression in normal immature thymocyte. We suggest that this response to interleukins may be part of a homeostatic mechanism to increase the production of immature thymocytes during stress.

Warm white LEDs with a high color rendering index and a low correlated color temperature have undergone rapid development. In this regard, red-emitting materials-such as fluoride phosphors, namely, A2MF6:Mn(4+) (A = K, Na, and Cs; M = Si, Ge, Zr, Sn, and Ti) and XSiF6:Mn(4+) (X = Ba or Zn), nitridoaluminate phosphor (Sr[LiAl3N4]:Eu(2+)), and nanocrystals of cesium lead iodide perovskite (CsPbI3)-have been extensively investigated recently. These compounds generate narrow emissions in the visible red spectral region that are highly perceived by the human eye and lead to excellent chromatic saturation of the red spectra. This paper describes the structure, luminescence properties, morphologies, thermal features, and moisture resistance of critical red components, as well as their limitations for practical applications. This Perspective also provides a basis for future development and scientific challenges in optical research.

To estimate the phylogenetic relationship of polyploid Hystrix in Triticeae, two single-copy nuclear genes (Acc1 and DMC1) and chloroplast trnL-F sequences of six Hystrix taxa were analyzed with those of nine Leymus species (NsXm), four Elymus species (StH) and 13 diploid taxa from seven monogenomic genera. Phylogenetic analyses reveal that Hystrix taxa contain two distinct types of genome constitution, despite the overall morphological and ecological similarity among Hystrix taxa. One type of genome constitution is StH (Hy. patula) as Elymus, the other is NsXm (Hy. californica, Hy. coreana, Hy. duthiei, Hy. duthiei ssp. longearistata and Hy. komarovii) as Leymus. The St, H and Ns genomes in Hystrix are donated by Pseudoroegneria, Hordeum and Psathyrostachys, respectively. The donor of the Xm genome is closely related to Agropyron (P). The trnL-F data especially indicate that there has been a maternal haplotype polymorphism in Hystrix species. Based on these results, we suggest that Hy. coreana, Hy. duthiei, Hy. duthiei ssp. longearistata, Hy. komarovii and Hy. californica should be included in the genus Leymus, and Hy. patula in the genus Elymus.

Transrectal biopsy of the prostate is necessary in the diagnosis of prostate cancer (PC). Though generally considered safe, patients encounter minor complications such as bleeding and urinary symptoms, and uncommonly, serious infections that may require antibiotic therapy, visits to the emergency room (ER) or hospital admission, causing morbidity and rarely even mortality. It is concerning that infections are on the rise due to resistant bacteria. Urologists will have to be aware of bacterial susceptibility studies to reduce such complications. This review focuses on prostate biopsy and its complications, and measures to reduce these complications in our practice.

The objective of this study was to evaluate relationships between quantitative EEG (qEEG) changes and cognitive disturbance (mild cognitive impairment or dementia) and the motor disturbance stage in Parkinson's disease (PD). Thirty-two PD patients (age = 67.2 +/- 10.0) and 26 normal subjects (age = 68.4 +/- 4.7) were assessed using a neurological evaluation, modified Hoehn and Yahr (HY) scale for PD, a Portuguese version of the CERAD neuropsychological battery (consortium to establish a registry for Alzheimer's disease) incorporating the Mini-mental Status Examination, Clinical Dementia Rating and an EEG analysis of absolute and relative band amplitude at rest. Four groups were compared: three with PD (7 patients with dementia, 10 with mild cognitive impairment and 15 with no cognitive disturbances) and the control group. The qEEG showed no significant differences between the control group and PD patients without cognitive disturbance. Abnormalities on the qEEG were essentially associated with the occurrence of mild cognitive impairment or dementia in patients with PD. There was an increase in the absolute and relative posterior theta amplitude in the groups with mild cognitive impairment or dementia and of the posterior absolute and relative delta amplitude in the group with dementia This study suggested qEEG as a possible physiological tool in the assessment of cognitive aspects in PD.

Borrowing principles of anhydrobiosis, we have developed a technique for self-assembling proteolipid-supported membranes on demand--simply by adding water. Intact lipid- and proteolipid vesicles dispersed in aqueous solutions of anhydrobiotic trehalose are vitrified on arbitrary substrates, producing glassy coats encapsulating biomolecules. Previous efforts establish that these carbohydrate coats arrest molecular mobilities and preserve native conformations and aggregative states of the embedded biomolecules, thereby enabling long-term storage. Subsequent rehydration, even after an extended period of time (e.g., weeks), devitrifies sugar--releasing the cargo and unmasking the substrate surface--thus triggering substrate-mediated vesicle fusion in real time, producing supported membranes. Using this method, arrays of membranes, including those functionalized with membrane proteins, can be readily produced in situ by spatially addressing vitrification using common patterning tools--useful for multiplexed or stochastic sensing and assaying of target interactions with the fluid and functional membrane surface.

Critical periods for experience-dependent plasticity are ubiquitous. The idea that experience-dependent plasticity is closely linked with the development of sensory function is still widely held; however, there also is growing evidence for plasticity in the adult nervous system. This article reviews the notion of a critical period for the treatment of amblyopia in light of recent experimental and clinical evidence for neural plasticity. Specifically, adults with amblyopia can improve their perceptual performance via extensive practice on a challenging visual task, and this improvement may transfer to improved visual acuity. Amblyopes achieve this improvement via the mechanisms that have been shown to explain perceptual learning in the normal visual system. It is hypothesized that these same mechanisms account for at least some of the improvement that occurs in the treatment of amblyopia.

Multi-locus sequence analysis has been demonstrated to be a useful tool for identification of Streptomyces species and was previously applied to phylogenetically differentiate the type strains of species pathogenic on potatoes (Solanum tuberosum L.). The ARS Culture Collection (NRRL) contains 43 strains identified as Streptomyces scabiei deposited at various times since the 1950s and these were subjected to multi-locus sequence analysis utilising partial sequences of the house-keeping genes atpD, gyrB, recA, rpoB and trpB. Phylogenetic analyses confirmed the identity of 17 of these strains as Streptomyces scabiei, 9 of the strains as the potato-pathogenic species Streptomyces europaeiscabiei and 6 strains as potentially new phytopathogenic species. Of the 16 other strains, 12 were identified as members of previously described non-pathogenic Streptomyces species while the remaining 4 strains may represent heretofore unrecognised non-pathogenic species. This study demonstrated the value of this technique for the relatively rapid, simple and sensitive molecular identification of Streptomyces strains held in culture collections.

The ability of a mass-balance algorithm to predict non-steady-state phenytoin concentrations in neurosurgery patients was compared with that of Phenda, a computerized Bayesian regression analysis program. Fifty neurosurgery patients who had had two or more initial phenytoin serum concentrations measured at least 60 hours apart and at least 1 hour after any i.v. doses, with the second concentration being not more than twice and not less than half of the first, and who had had a third or final phenytoin measurement (for use in a prediction analysis) were evaluated. The patients' maximum rates of metabolism were calculated by using the two initial phenytoin concentrations and a mass-balance algorithm, and the third phenytoin concentration was predicted. The patients' demographics and phenytoin dosages and concentrations were entered into Phenda, which was used to predict the third phenytoin concentration. The ability of the two methods to predict the third concentration was evaluated by the method of Sheiner and Beal. Fifty observations from 48 patients were evaluated. The mass-balance algorithm had a positive prediction bias of 2.52 mg/L and a precision error of 5.08 mg/L, compared with 2.30 and 5.30, respectively, for Phenda. The difference in the results between the two methods was not significant. There was no significant difference between the mass-balance algorithm and Phenda in the ability to predict phenytoin concentrations.

A case of atraumatic arteriovenous (AV) fistula of the extracranial vertebral artery associated with an atraumatic aneurysm of the contralateral extracranial vertebral artery is reported. The fistulous lesion was excised after distal and proximal ligation of the vessel. Subsequently, the contralateral aneurysm underwent spontaneous dissolution. Seven cases of extracranial vertebral AV fistulae associated with ipsilateral vertebral artery aneurysms (four traumatic and three as part of vascular dysplastic syndromes) have been reported previously.

3-Butene-1,2-diol (butenediol), a major metabolite of 1,3-butadiene (butadiene), can undergo either detoxification or biotransformation to potentially toxic metabolites, including 3,4-epoxy-1,2-butanediol and hydroxymethylvinyl ketone (HMVK). Butadiene exposure can occur concomitantly with hexanes, which share common biotransformation pathways with butadiene. To determine the potential influence of hexane co-exposure on butadiene toxicity, the present study examined the effect of n-hexane on butenediol disposition [as measured by urinary excretion of (N-acetyl-S-(3,4-dihydroxybutyl)-L-cysteine) (MI level)] and genotoxicity (as measured by the frequency of bone marrow micronucleated erythrocytes) and acute toxicity (as measured by body weight changes) in the rat. The results show that butenediol was not genotoxic to adult or immature rats but was acutely toxic to adult but not immature rats. The results also suggest that n-hexane co-exposure may attenuate the acute toxicity by butenediol in adult rats and that immature rats may be less sensitive than adults to the acute toxicity.

In cod, Gadus morhua L., calcium levels expressed as percentage of tissue dry weight were (mean +/- SD) 0.0042 +/- 0.0010% of ovary before final maturation and 0.0133 +/- 0.0024% of mature eggs. In plaice Pleuronectes platessa L. these values were 0.0029 +/- 0.0006 and 0.0097 +/- 0.0001. In mature eggs of both fish species these values are at least one order of magnitude less than in the yolk of the domestic fowl Gallus domesticus L. (0.14% of dry weight). The corresponding values for iron were (2.31 +/- 0.22) X 10(-3)% of ovary and (3.07 +/- 0.29) X 10(-3)% of mature egg in cod. In plaice these values were (1.57 +/- 0.15) X 10(-3)% and (2.74 +/- 0.94) X 10(-3)%. These levels are 4-7 times less than in the yolk of the domestic fowl (0.012-0.020%). These differences between the mature pelagic eggs of marine teleosts and the eggs of other oviparous vertebrates appear to be related to the availability of these elements in sea water, the different nature of the yolk phosphoprotein and the lower levels of protein phosphorus in the eggs of these fish species.

The potency of parasympathetic vasomotor efferent nerves in controlling blood flow of the face and nose was indicated by the following features attributed to the maxillary artery and their vascular compartments in dogs. Electrical stimulation of the vidian nerve induced a frequency-dependent increase in maxillary flow, which was due to a significant decrease in resistance to flow in nutrient and shunt vessels. Pronounced increases in perfusion rates mainly occurred in evaporative tissues of the nose, in particular the naso-maxilloturbinates and alar fold during vidian nerve stimulation, while those, for example, of the skin remained unchanged. Adrenergic and subsequent cholinergic blockade left the response pattern of maxillary flow to vidian nerve stimulation basically unaffected. Both nutrient and shunt flows contributed to the parasympathetically induced increases in maxillary flow while responses were compartmentalized similar to that found in untreated animals. Apart from sympathetic vasoconstrictor inputs, these results show that cholinergic and non-cholinergic parasympathetic vasodilator inputs contribute to the adjustment of vasomotor tone in the maxillary vascular bed.

Bileduct catheterisation percutaneously through the liver can be used in patients with obstructive jaundice as an adjunct or as an alternative to surgery. Preoperative drainage allows adequate treatment of severe cholangitis and reduces jaundice. Palliative drainage, whether internal or external, can be used instead of surgery. Drainage through the liver succeeded in 40 of 41 patients. Two complications followed the procedure and were treated conservatively. Bile drainage was established through an endoprosthesis into the duodenum in 7 patients and externally through a catheter in the remaining 33. The technique is described, and its use in patients with suppurative cholangitis and benign and malignant biliary strictures is illustrated.

Obesity is a major risk factor for multiple severe health conditions, including cardiovascular diseases, diabetes and cancer. It is often related to an increased risk of morbidity and mortality and, as it can be accompanied by non-fatal health problems, quality of life is seriously reduced due to related conditions including hypertension, sleep apnea, osteoarthritis, respiratory problems and infertility. Evidence suggests that oxidative stress is related to obesity and its complications. In obese patients, there is an increase in levels of reactive oxygen species and nitrogen species and antioxidant defenses are undermined in comparison to normal-weight counterparts. In addition, these parameters inversely correlate with central adiposity. In this review, the authors discuss current concepts concerning the relationship between obesity and oxidative stress and mitochondrial impairment. Potential interventions to improve redox balance are also explored.

The product of the EUG1 gene of Saccharomyces cerevisiae is a soluble endoplasmic reticulum protein with homology to both the mammalian protein disulfide isomerase (PDI) and the yeast PDI homolog encoded by the essential PDI1 gene. Deletion or overexpression of EUG1 causes no growth defects under a variety of conditions. EUG1 mRNA and protein levels are dramatically increased in response to the accumulation of native or unglycosylated proteins in the endoplasmic reticulum. Overexpression of the EUG1 gene allows yeast cells to grow in the absence of the PDI1 gene product. Depletion of the PDI1 protein in Saccharomyces cerevisiae causes a soluble vacuolar glycoprotein to accumulate in its endoplasmic reticulum form, and this phenotype is only partially relieved by the overexpression of EUG1. Taken together, our results indicate that PDI1 and EUG1 encode functionally related proteins that are likely to be involved in interacting with nascent polypeptides in the yeast endoplasmic reticulum.

The glycosylated hemoglobin (glyco Hb) and the glycoprotein of the plasma were determined using affinity chromatographic techniques in cord blood and maternal blood of normal (Group I), White's Class A diabetic (Group II), and insulin-dependent diabetic (Group III) mothers. The results revealed significant increase of glyco Hb (P less than 0.005) and glycoprotein (P less than 0.005) in the newborns of Group III mothers in comparison to those of Group I. The glyco Hb of maternal blood in this group also showed significant increase (P less than 0.005) while the increase in Hb A1 and plasma glycoprotein were nonsignificant. All values for cord blood and maternal blood of White's Class A diabetics revealed no significant change from the normal group. We conclude that the fetuses of insulin-dependent diabetic mothers are hyperglycemic in utero.

Various inbred mouse strains showed remarkable conservation of organization in the epsilon germline region as determined by restriction mapping. Restriction fragment length polymorphisms (RFLP) were seen in the epsilon gene region for only two of eight restriction enzymes tested. Furthermore, the RFLP did not correlate with the IgE-response phenotype for the murine strains SJL, SJA, C57BL/6, BALB/c, A/ST, and A/J. The IgE class-switch region (S epsilon) DNA from an SJL genomic clone was sequenced and was compared with S epsilon sequences from BALB/c mice. These S epsilon sequences were at least 95% homologous. Most of the S epsilon sequence differences observed between the two strains were single base pair substitutions, deletions, or insertions. The largest difference between the S epsilon sequences resulted from an insertion of seven contiguous bases seen in the SJL S epsilon region.

A space-time model of health requires a profound re-thinking of many of our basic tenets. This modern view of man and his world discards the traditional mechanistic paradigm which has been the focus of Western scientific thought and medicine. Stress related disorders are thought to be a result in part of an individual's perception of linear time. Holistic strategies such as biofeedback, relaxation skills, hypnosis, yoga, and imagery, to name a few, ask the individual to step outside linear or objective time by expanding their sense of experiential or subjective time and consciousness. It is suggested that training the time sense is a tool of holistic medicine and a space-time model of health.

Natural variation of the levorin-producing organism Act. levoris, strain 28 was studied with respect to the colony morphology and production of levorin and levoristatin. The population of strain 28 consisted of 3 morphological colony types, the main type amounting to 99.7 percent. The strain variation with respect to production of levorin and levoristatin ranged from 20 to 180 and from 0 to 300 percent respectively as compared to the control. Mutant M-28 differing from the initial strain by the colony morphology, moderate phage titer and preferable production of levoristatin was isolated as a result of repeated passages of strain 28 onto agarized Chapek media with starch without maintaining selection. Variants differing from the population of strains 28 and M-28 by the ratio of levorin and levoristatin in the culture fluid were selected. No correlation in production of the above antibiotics by strain 28 was noted. Preparations obtained with strain M-28 differed from those obtained with strain 28 in a significant content of levoristatin.

Chymopapain (1 mg) was injected into each of four-lumbar intervertebral discs of adult mongrel dogs. As expected, at 2 weeks, all injected discs exhibited marked loss of height (mean: 50% of original height) indicative of severe proteoglycan depletion. The appearance of keratan sulfate-bearing fragments in plasma was monitored by an ELISA-inhibition assay which uses a monoclonal antibody (1/20/5-D-4) specific for an epitope present only in the longest keratan sulfate chains. Levels of plasma keratan sulfate rose within 30 minutes and reached a maximum between 24 and 72 hours later. Levels then declined progressively but were still elevated at 2 weeks postinjection. Keratan sulfate-bearing fragments in plasma were purified by ion exchange chromatography on DEAE-Sephacryl and fractionated by sieve chromatography on Sepharose CL-6B. These plasma keratan sulfate-bearing fragments were found to be similar in size to keratan sulfate-bearing fragments generated by chymopapain digestion of dog nucleus pulposus proteoglycans, but slightly larger than single keratan sulfate chains obtained by alkaline borohydride treatment of dog nucleus pulposus proteoglycans. The results of this study show that measurements of blood levels of keratan sulfate could prove useful in monitoring effective degradation of disc proteoglycans in chemonucleolysis in man and help discriminate between ineffective enzyme placement, and alternative mechanisms of treatment failure.

Our understanding of the pathogenesis of multiple sclerosis has increased considerably, leading to the development of novel therapeutic approaches and compounds. Several agents have undergone clinical testing and have recently received market authorization or are being evaluated for approval. Alemtuzumab is a humanized monoclonal antibody that rapidly depletes CD52+ cells of the lymphoid lineage from peripheral blood, but spares lymphoid precursor cells. Clinical efficacy and safety data from clinical phase II and III trials-all using interferon-β-1a as active comparator-are summarized and placed in perspective. This review further analyzes the differential reconstitution of T and B cells as a potential mode of action and the pathogenic link to treatment-emergent secondary autoimmune conditions. Given recent positive opinions by regulatory agencies, this new drug will be positioned for the treatment of active relapsing-remitting multiple sclerosis and enlarge our therapeutic armamentarium.

We recorded the pulsed jet Fourier transform microwave spectrum of the 1 : 1 adduct of CH2ClF with formaldehyde. Formaldehyde is linked to CH2ClF through a C-H···Cl bond rather than a weak C-H···F hydrogen bond, with a H···Cl "bond length" of 2.918 Å. Two additional equivalent C-H···O contacts, with a H···O distance of 2.821 Å, characterize the complex. Tunnelling splittings due to the internal rotation of the formaldehyde moiety have been observed, which allowed estimating the barrier to the internal rotation of formaldehyde to be 125(10) cm(-1). The (35)Cl quadrupole coupling constants have been determined to be χaa = 31.131(7) MHz and χbb-χcc = -105.82(1) MHz.

Molecular orientation in thin films of a rigid rod conjugated polymer, a derivative of poly(para-phenylene ethynylene)s with linear side chains and thioacetyl end groups, was investigated by reflection-absorption infrared spectroscopy and X-ray diffraction technique. The results indicated that TA-PPE molecules tended to align with their backbone planes perpendicular to substrates, that is, with an "edge-on" molecular orientation in the films. Such molecular orientation is favorable for the efficient carrier transport in two-dimensional direction in the polymer films (i.e., via both the intrachain and interchain), so that high performance organic field-effect transistors were fabricated with hole mobility at around approximately 4.3 x 10(-3) cm(2)/Vs.

Dietary proteins elicit a wide range of nutritional and biological functions. Beyond their nutritional role as the source of amino acids for protein synthesis, they are instrumental in the regulation of food intake, glucose and lipid metabolism, blood pressure, bone metabolism and immune function. The interaction of dietary proteins and their products of digestion with the regulatory functions of the gastrointestinal (GI) tract plays a dominant role in determining the physiological properties of proteins. The site of interaction is widespread, from the oral cavity to the colon. The characteristics of proteins that influence their interaction with the GI tract in a source-dependent manner include their physico-chemical properties, their amino acid composition and sequence, their bioactive peptides, their digestion kinetics and also the non-protein bioactive components conjugated with them. Within the GI tract, these products affect several regulatory functions by interacting with receptors releasing hormones, affecting stomach emptying and GI transport and absorption, transmitting neural signals to the brain, and modifying the microflora. This review discusses the interaction of dietary proteins during digestion and absorption with the physiological and metabolic functions of the GI tract, and illustrates the importance of this interaction in the regulation of amino acid, glucose, lipid metabolism, and food intake.

Fractures of the thoracic spine (T2-T12) should be considered as a separate entity because of the anatomic features of the rib cage and spinal canal in this region. Fifty-seven patients sustained this injury over a 10-year period (16% of thoracic, thoracolumbar, and lumbar fractures). Twenty-eight fracture dislocations, 25 compression fractures, and 1 burst fracture were seen. Three injuries, combining elements of a burst fracture and a dislocation, were designated "burst-dislocations." Apart from compression fractures, a direct blow was often the implicated mechanism of injury. Significant associated injuries were uncommon. Fracture-dislocations were often associated with neurologic injury and compression fractures with long-term pain. Operative treatment appeared to afford the best results for stabilization and pain relief.

Due to the plethora of pharmacological activities reported in the literature, <i>Origanum vulgare</i> L. is a valuable aromatic plant for the medicine of the XXI century. Recent studies highlight that <i>Origanum vulgare</i> L. essential oil (OvEo) has gained attention in the dermatological field due to the cosmeceutical potential correlated with the presence of thymol and carvacrol. As a result of the fulminant expansion of bacterial resistance to antibiotics and the aggressiveness of skin infections, OvEo was extensively studied for its antimicrobial activity against <i>Staphyloccocus</i> spp. and <i>Pseudomonas aeruginosa</i>. Moreover, researchers have also assessed the anti-inflammatory activity of OvEo, suggesting its tissue remodeling and wound healing potential. Whereas OvEo comprises important biological activities that are used in a wide range of pathologies, recently, essential oils have shown great potential in the development of new therapeutic alternatives for skin disorders, such as acne, wounds or aging. Furthermore, substantial efforts have been committed to the development of modern formulations, such as microemulsions and nanoemulsions, in order to create the possibility for topical application. The review brings to the fore the most recent findings in the dermatological field regarding potential plant-based therapies involving OvEo, emphasizing the modern pharmaceutical formulation approaches and the cutaneous benefits in skin disorders.

An 82-year-old female was referred to our hospital because of low-grade fever, anemia, and rapidly progressive nephritic syndrome. Her laboratory data showed mild proteinuria, mild renal failure, and the presence of myeloperoxidase-specific anti-neutrophil cytoplasmic autoantibody. A skin biopsy specimen taken from the erythematous purpura revealed neutrophilic infiltration around the blood vessels with fibrinoid changes in the vessel walls. A renal biopsy specimen revealed segmental necrotizing glomerulonephritis with fibro-cellular crescent formation without deposits of immunoglobulin or complement components, indicating microscopic polyangiitis. The use of corticosteroid treatment, including intravenous methylprednisolone, improved renal failure. After 4 years with low-dose maintenance corticosteroid therapy, she developed de novo acute hepatitis B, and entecavir was remarkably effective, showing a rapid recovery from liver dysfunction with jaundice. To prevent hepatitis B virus (HBV) reactivation and de novo acute hepatitis B induced by immunosuppressive or cytotoxic therapy, including corticosteroids alone, the measurement of HBV-related serological markers needs to be performed prior to the initiation of such therapy, even in renal diseases.

This work investigated the effects of hot air drying pretreatment (HAD), freeze drying pretreatment (FD) and vacuum drying pretreatment (VD) on the physicochemical properties and structural characterizations of starch isolated from canistels. X-ray diffraction displayed that the starches separated from canistel by different drying pretreatments showed a typical A-type crystal structure. The SEM image showed that cracks and debris appeared on the surface of HVD and VD particles. The molecular structure of starches obtained by different drying pretreatments was studied using Fourier infrared and solid state ¹³C CP/MAS NMR analysis. The results indicated that vacuum drying pretreatment could promote the formation of the double helix of starch granules, and hot air drying and freeze drying destroyed the ordered structure of starch granules. These structural changed to affect the physicochemical properties of starch granules. The study of different drying pretreatments to separate starches provided practical value for drying pretreatments. Furthermore, the current study affords information for canistel starches cultivated in China that would be convenient for commercial applications.

The Cdc6 protein, a key DNA replication initiation factor, contributes to the long-term maintenance of the S-phase checkpoint by anchoring the Rad3-Rad26 complex to chromatin. Here, we demonstrate that ATR (AT mutated and Rad3 related) activity is essential for maintaining high chromatin levels of the Cdc6 protein, thereby delaying entry into mitosis during hydroxyurea (HU)-induced S-phase arrest of HeLa cells. Downregulation of ATR (AT mutated and Rad3 related) (i.e., using ATR-siRNA) reduced the protein levels of chromatin Cdc6 and significantly increased the cellular levels of phospho-histone H3 (Ser 10), an index of mitosis. Downregulation of Cdc6 was completely restored by pretreatment with MG132, a proteasome inhibitor. Moreover, mitotic entry of MG132-pretreated cells was significantly downregulated. Our results also show that ATR (AT mutated and Rad3 related) kinase phosphorylates Cdc6 at serine residue 6. Thus, this ATR (AT mutated and Rad3 related)-mediated phosphorylation of Cdc6 is likely associated with stabilization of Cdc6 protein, thereby maintaining high levels of chromatin Cdc6 and delaying premature mitotic entry. This novel mechanism likely contributes to the functional regulation of chromatin Cdc6, which delays the cell cycle of hydroxyurea-induced cells to enter mitosis at the S-phase checkpoint.

We derive and employ a local potential to represent the Fock exchange operator in electronic single-particle equations. This local Fock-exchange (LFX) potential is very similar to the exact exchange (EXX) potential in density functional theory (DFT). The practical software implementation of the two potentials (LFX and EXX) yields robust and accurate results for a variety of systems (semiconductors, transition metal oxides) where Hartree-Fock and popular approximations of DFT typically fail. This includes examples traditionally considered qualitatively inaccessible to calculations that omit correlation.