Abnormal spiral arteries modification in stillbirths: the role of maternal prepregnancy body mass index.
To evaluate the prevalence of abnormal spiral arteries modification (ASAM) in stillbirths and its anatomo-clinical correlations. Two-hundred and three placentas of stillbirth ≥20 weeks of gestation were analyzed. ASAM was present in 69/203 cases (33.9%). The only maternal characteristic that significantly differed in ASAM versus normal spiral arteries modification (NSAM) cases was the prepregnancy body mass index (BMI) (25.9 ± 6.1 and 23.1 ± 4.2 kg/m(2), respectively) with 15.9% of obesity in ASAM mothers versus 5.2% in NSAM (p = 0.02). Given the association between obesity and adverse pregnancy outcome, our data suggest that counselling obese women to lose weight before pregnancy becomes increasingly imperative.


[Fungal flora in mycoses among the population of the south-eastern Poland 1978-1988].
In the years 1978-1988 a group of 2257 subjects was examined for the presence of fungal infection. In 785 cases positive results of cultures were obtained yielding 468 dermatophytes (60.1%) and 317 yeast-like fungi (39.9%). The most frequently isolated fungi were: Candida albicans (27.3%), Trichophyton mentagrophytes v. interdigitale (27.0%) and Trichophyton rubrum (20.6%). In the subgroup of dermatophytes anthropophilic fungi accounted for 87.5%.


Leaving group and gas phase neighboring group effects in the side chain losses from protonated serine and its derivatives.
The gas phase fragmentation reactions of protonated serine and its YNHCH(CH2X)CO2H derivatives, beta-chloroalanine, S-methyl cysteine, O-methyl serine, and O-phosphoserine, as well as the corresponding N-acetyl model peptides have been examined via electrospray ionization tandem mass spectrometry (MS/MS). In particular, the competition between losses from the side chain and the combined loss of H2O and CO from the C-terminal carboxyl group of the amino acids or H2O or CH2CO from the N-acetyl model peptides are compared. In this manner the effect of the leaving group (Y = H or CH3CO, vary X) or of the neighboring group can be examined. It was found that the amount of HX lost from the side chain increases with the proton affinity of X [OP(O)(OH)2 > OCH3 approximately equals OH > Cl]. The ion due to the side chain loss of H2O from the model peptide N-acetyl serine is more abundant than that from protonated serine, suggesting that the N-acetyl group is a better neighboring group than the amino group. Ab initio calculations at the MP2(FC)/6-31G*//HF/6-31G* level of theory suggest that this effect is due to the transition state barrier for water loss from protonated N-acetyl serine being lower than that for protonated serine. The mechanism for side chain loss has been examined using MS3 tandem mass spectrometry, independent synthesis of proposed product ion structures combined with MS/MS, and hydrogen/deuterium exchange. Neighboring group rather than cis 1,2 elimination processes dominate in all cases. In particular, the loss of H3PO4 from O-phosphoserine and N-acetyl O-phosphoserine is shown to yield a 3-membered aziridine ring and 5-membered oxazoline ring, respectively, and not the dehydroalanine moiety. This is in contrast to results presented by DeGnore and Qin (J. Am. Soc. Mass Spectrom. 1998, 9, 1175-1188) for the loss of H3PO4 from larger peptides, where dehydroalanine was observed. Alternate mechanisms to cis 1,2 elimination, for the formation of dehydroalanine in larger phosphoserine or phosphothreonine containing peptides, are proposed.


Biosynthesis of reovirus-specified polypeptides: effect of point mutation of the sequences flanking the 5'-proximal AUG initiator codons of the reovirus S1 and S4 genes on the efficiency of mRNA translation.
The effect on translation of site-directed nucleotide substitutions around the 5'-proximal AUG initiation codon of the reovirus s1 mRNA specifying polypeptide sigma 1 and the reovirus s4 mRNA specifying polypeptide sigma 3 was examined. The efficiency of synthesis of the S1-encoded sigma 1 polypeptide and the S4-encoded sigma 3 polypeptide was analyzed in transfected simian COS cells. Mutant s1 mRNAs possessing either GCU AUG G or GCA AUG G sequences surrounding the 5'-proximal sigma 1 AUG were translated with an efficiency comparable to that of the wild-type s1 mRNA which possesses the flanking sequence CCU AUG G. Mutant s4 mRNAs possessing either CCU AUG G or CCA AUG G sequences surrounding the 5'-proximal sigma 3 AUG were translated with an efficiency comparable to that of wild-type s4 mRNA which possesses the flanking sequence GCA AUG G. The s4 mRNAs, both wild-type and mutant, were translated in vivo about five times more efficiently than the s1 mRNAs, both wild-type and mutant. These results suggest that nucleotide positions other than the -3, -2, -1, and +4 positions relative to the 5'-proximal initiator AUG, where the A is +1, play a dominant role in determining the efficiency of translation of these two reovirus mRNAs in vivo.


Thermodynamics and kinetics of the hydrolysis and resynthesis of the reactive site peptide bond in turkey ovomucoid third domain by aspergillopeptidase B.
1. Aspergillopeptidase B rapidly hydrolyses the -Leu18-Glu19-reactive site peptide bond in turkey ovomucoid third domain (OMTKY3) within the pH-range of 4.0-8.4. The reaction proceeds to equilibrium between OMTKY3 and its modified form with the reactive site peptide bond cleaved (OMTKY3). 2. The dependence of the equilibrium constant (Khyd) on pH indicates that hydrolysis of the reactive site peptide bond apparently does not perturb the pK-values of any preexistent ionizable groups in OMTKY3. 3. The obtained Khyd0 value indicates that free energies of OMTKY3 and OMTKY3 are essentially the same. 4. Hydrolysis of the reactive site peptide bond by aspergillopeptidase B at neutral pH is about 60 times faster than the same reaction catalyzed by subtilisin (Carlsberg), the enzyme strongly inhibited by OMTKY3. 5. Resynthesis of the reactive site peptide bond at neutral pH catalyzed by aspergillopeptidase B (reverse reaction) is almost four orders of magnitude faster than the forward reaction.


Leptin signaling and aging: insight from caloric restriction.
Organisms have evolved neuroendocrine and metabolic response systems to enhance survival during periods of food shortage, which occur frequently in nature. The anti-aging effect of caloric restriction (CR) might derive from these adaptive responses to maximize organism survival. The present article discusses the potential role for leptin, a hormone secreted from adipocytes, as a key signal that induces the adaptive responses relevant to CR. Evidence indicates that a CR-induced reduction of the plasma leptin concentration suppresses the gonadal, somatotropic, and thyroidal axes, and activates the adrenal axis. Metabolic adaptation, a shift in fuel utilization mainly conducted in the liver, seems to require leptin signaling. Although alternative signaling pathways might also mediate the anti-aging effects of CR, leptin signaling could be a substantial pathway involved in these effects. Molecular dissection of the mechanisms underlying the effects of CR will contribute to a better understanding of the aging process, leading to the extension of a healthy lifespan in humans.


Birth in standing position: a high frequency of third degree tears.
During the past years a major change in the use of delivery position has occurred in Sweden. Recumbent delivery positions have been replaced by a variety of positions: squatting, standing, lateral, kneeling and quadruped. The consequences of this shift in obstetrical practice for development of perineal lacerations are largely unknown. Retrospective comparison of uncomplicated deliveries in standing (n = 650) and sitting (n = 264) position with respect to third degree lacerations. The standing and sitting delivery group were similar with respect to maternal, infant and delivery characteristics. The frequency of third degree tears was 2.50% in standing and 0.38% in sitting birth position (p < 0.05). In nulliparous women, third degree tears occurred in 4.2% in standing and 1.0% in sitting position. The present data implies that the risk of third degree lacerations is considerably higher (7 x) in standing than in sitting birth positions.


On the Dominance of Attitude Emotionality.
Many situations in our lives require us to make relatively quick decisions as whether to approach or avoid a person or object, buy or pass on a product, or accept or reject an offer. These decisions are particularly difficult when there are both positive and negative aspects to the object. How do people go about navigating this conflict to come to a summary judgment? Using the Evaluative Lexicon (EL), we demonstrate across three studies, 7,700 attitude expressions, and nearly 50 different attitude objects that when positivity and negativity conflict, the valence that is based more on emotion is more likely to dominate. Furthermore, individuals are also more consistent in the expression of their univalent summary judgments when they involve greater emotionality. In sum, valence that is based on emotion tends to dominate when resolving ambivalence and also helps individuals to remain consistent when offering quick judgments.


Axonal gap junctions send ripples through the hippocampus.
In a paper by Schmitz and colleagues in this issue of Neuron, new evidence for the existence of gap junctions between pyramidal cell axons uncovers a mechanism for fast neural communication in the hippocampus. Electrical coupling between axons may be crucial during fast oscillations, which have been proposed to mediate memory consolidation.


Theoretical studies on the structures, thermodynamic properties, detonation properties, and pyrolysis mechanisms of spiro nitramines.
Density function theory (DFT) has been employed to study the geometric and electronic structures of a series of spiro nitramines at the B3LYP/6-31G level. The calculated results agree reasonably with available experimental data. Thermodynamic properties derived from the infrared spectra on the basis of statistical thermodynamic principles are linearly correlated with the number of nitramine groups as well as the temperature. Detonation performances were evaluated by the Kamlet-Jacobs equations based on the calculated densities and heats of formation. It is found that some compounds with the predicted densities of ca. 1.9 g/cm3, detonation velocities over 9 km/s, and detonation pressures of about 39 GPa (some even over 40 GPa) may be novel potential candidates of high energy density materials (HEDMs). Thermal stability and the pyrolysis mechanism of the title compounds were investigated by calculating the bond dissociation energies (BDE) at the B3LYP/6-31G level and the activation energies (E(a)) with the selected PM3 semiempirical molecular orbital (MO) based on the unrestricted Hartree-Fock model. The relationships between BDE, E(a), and the electronic structures of the spiro nitramines were discussed in detail. Thermal stabilities and decomposition mechanisms of the title compounds derived from the B3LYP/6-31G BDE and the UHF-PM3 E(a) are basically consistent. Considering the thermal stability, TNSHe (tetranitrotetraazaspirohexane), TNSH (tetranitrotetraazaspiroheptane), and TNSO (tetranitrotetraazaspirooctane) are recommended as the preferred candidates of HEDMs. These results may provide basic information for the molecular design of HEDMs.


[The influence of calcineurin gene polymorphism on morphofunctional characteristics of cardiovascular system of athletes].
The aim of the study was to investigate allelic distribution of calcineurin gene (CNB; 5I/5D polymorphism) in athletes of cyclic sports (n = 673) and controls (n = 1073), and to find interrelation between genotypes and risk of left ventricular hypertrophy and physical performance of athletes. Genotyping was performed by restriction fragment length polymorphism. Echocardiography was performed by ultrasound scanner Aloka-3500. Physiological parameters were evaluated by spiroergometry using MetaMax 3B Gas Analyzer. The frequency of CNB D allele was significantly lo- wer in athletes than in controls (5.5 vs. 8.8 %; p = 0.0005), and decreased with the growth of skills. We found that CNB D allele was associated with increased left ventricular mass index and low values of physical performance (when maximal power production capacity and maximal oxygen consumption were measured). Thus, CNB gene 5I/5D polymorphism is associated with the risk of left ventricular hypertrophy and physical performance of athletes.


[Arthroplasty according to colonna - 1999.].
Authors evaluate results of arthroplasty according to Colonna.The surgery was performed at the Ist University department of orthopaedics in Bratislava in the period of 1955-1973. Of 97 patients (123 hips), 64 (79 hips) were followed up 5-25 years and 23 (31 hips) over 25 years. All patients at the last follow up for were assessed as having not satisfactory results, because of early pain at the operated side, limited movement of the hip joint and radiologically evident arthritic changes. Key words: Colonna, arthroplasty, DDH.


Combination radioimmunotherapy with local hyperthermia: increased delivery of radioimmunoconjugate by vascular effect and its retention by increased antigen expression in colon cancer xenografts.
Hyperthermia (HT) may increase tumor targeting of a radiolabeled antibody by its effects on tumor vasculature and antigen expression. Expression of a 45-kDa glycoprotein antigen on LS180 colon cancer cells was 2.7-fold enhanced 2 days after heating at 43 degrees C for 1 h. Preferential tumor accumulation of 125I-A7 recognizing this antigen was doubled and the antitumor effect of 131I-A7 was significantly improved by HT. Hyperthermia also increased tumor uptake of an irrelevant antibody but its radioactivity was rapidly cleared. These results indicate that HT increased the initial delivery of an antibody to a tumor by its vascular effect, and radioactivity was retained in tumors by increased specific binding, resulting in a better radioimmunotherapy outcome.


Identification of morin as an agonist of imidazoline I-3 receptor for insulin secretion in diabetic rats.
Morin is a flavonoid contained in guava that is known to reduce hyperglycemia in diabetics. Morin has been demonstrated to increase plasma insulin. However, the mechanism(s) remains unknown. The present study is designed to investigate the effect of morin on the imidazoline receptor (I-R) that regulates insulin secretion. We used Chinese hamster ovary (CHO) cells transfected with an I-R expression construct (NISCH-CHO-K1 cells) to identify the direct effect of morin on the I-R. Moreover, the imidazoline I3 receptor (I-3R) is known to be present in pancreatic β cells and involved in insulin secretion. Therefore, we applied a specific antagonist (KU14R) to block I-3R in diabetic rats. Additionally, the effect of morin on insulin secretion was characterized in isolated pancreatic islets. Morin decreased blood glucose levels by increasing plasma insulin levels in diabetic rats. In CHO cells expressing an I-R, morin increased calcium influx in a dose-dependent manner. Additionally, KU14R dose-dependently inhibited the morin-induced effects, including hypoglycemia and the increase in insulin secretion and plasma C-peptide levels, in diabetic rats. Furthermore, morin enhanced insulin secretion from isolated pancreatic islets, and this effect was also dose-dependently inhibited by KU14R. Phospholipase C (PLC) is known to couple with the I-R, and a PLC inhibitor dose-dependently attenuated the insulin secretion induced by morin in isolated pancreatic islets. Taken together, these data suggest that morin can activate I-3R to enhance insulin secretion. Therefore, it would be useful to develop morin into a treatment for diabetic disorders.


Hyperexpression of recombinant CFTR in heterologous cells alters its physiological properties.
We investigated whether high levels of expression of the cystic fibrosis transmembrane conductance regulator (CFTR) would alter the functional properties of newly synthesized recombinant proteins. COS-7, CFPAC-1, and A549 cells were intranuclearly injected with a Simian virus 40-driven pECE-CFTR plasmid and assayed for halide permeability using the 6-methoxy-N-(3-sulfopropyl)quinolinium fluorescent probe. With increasing numbers of microinjected pECE-CFTR copies, the baseline permeability to halide dose dependently increased, and the response to adenosine 3',5'-cyclic monophosphate (cAMP) stimulation decreased. In cells hyperexpressing CFTR, the high level of halide permeability was reduced when a cell metabolism poisoning cocktail was applied to decrease intracellular ATP and, inversely, was increased by orthovanadate. In CFPAC-1 cells investigated with the patch-clamp technique, CFTR hyperexpression led to a time-independent nonrectifying chloride current that was not sensitive to cAMP stimulation. CFPAC-1 cells hyperexpressing CFTR exhibited no outward rectifying chloride current nor inward rectifying potassium current either spontaneously or under cAMP stimulation. We conclude that hyperexpression of recombinant CFTR proteins modifies their properties inasmuch as 1) CFTR channels are permanently activated and not susceptible to cAMP regulation and 2) they lose their capacity to regulate heterologous ionic channels.


Is functional dependence of Duchenne muscular dystrophy patients determinant of the quality of life and burden of their caregivers?
The relationship between functional dependence and quality of life (QOL) in Duchenne muscular dystrophy (DMD) patients and burden and QOL in caregivers is not clear. This study investigated possible relationships between functional dependence/QOL of DMD patients and QOL/burden of caregivers. This study included 35 boys (6-17 years) and respective caregivers (above 21 years). Caregivers answered to World Health Organization Quality of Life and Zarit Burden Interview questionnaires. Patients were assessed with the Motor Function Measure and the Autoquestionnaire Qualité de vie Enfant Imagé. Spearman correlations and linear regressions were run to investigate relationships between the variables. The occurrence of lower QOL and higher burden among the caregivers of patients with Duchenne muscular dystrophy was evidenced. The functional dependence of patients was not considered a determinant factor. Higher caregivers' burden was related to lower caregivers' QOL and to higher patients' ages.


Fixation of ankle fragility fractures by tibiotalocalcaneal nail.
Fragility fractures of the ankle are difficult to treat by conventional fixation due to poor bone quality, compromised soft tissues, and inherent instability. Conservative management of these patients also has its problems. We retrospectively reviewed 13 patients who underwent intramedullary nailing through the tibiotalocalcaneal joints in an attempt to achieve the dual aims of fracture control and early mobilisation. The Olerud and Molander scale was used as outcome measures. There were 12 females and 1 male with a mean age of 78.9 (range 64-93). Half of the patients were discharged from hospital within the first 2 weeks after the operation. All achieved a comparable function to their pre-operative state. The mean follow-up period was 11 months (range of 2-62 months). Six are now deceased from unrelated causes. The mean Olerud and Molander score was 50 (range 30-65). All the radiographs showed evidence of fracture union with no changes in the overall alignment of the joint. Given the low survivorship of this frail group of patients the main objectives are achieving early mobilisation whilst maintaining good fracture position. In our experience, tibiotalocalcaneal nailing is a very useful and successful way of treating fragility fractures of the ankle because it has a low risk of complications and restores function with impressive patient satisfaction. The potential benefits of this technique, we believe, outweigh the disability ensued from subtalar joint fusion.


Intramedullary disseminated capillary hemangioma with localized spinal cord swelling: case report.
A case of intramedullary disseminated capillary hemangioma in the cervical spinal cord is presented. The patient showed progressive neurological deficits. Magnetic resonance imaging showed localized swelling of the spinal cord. This case was initially misdiagnosed at another institution as syringomyelia. Decompression of the posterior fossa and a syringo-subarachnoid shunt operation were performed. However, the operative findings in the authors' institution showed edematous tissue with no apparent neoplastic characteristics. Pathological findings revealed angiomatous nests consisting of small capillary-like vessels, telangiectatic vessels, and aggregated venules scattered in the edematous and partially necrotic spinal cord tissue. The edema and necrosis of the cervical cord were considered to have been caused by circulatory disturbances in the spinal cord parenchyma resulting from these vascular lesions.


Minority perceptions of Whites' motives for responding without prejudice: the perceived internal and external motivation to avoid prejudice scales.
Whites' nonprejudiced behavior toward racial/ethnic minorities can be attributionally ambiguous for perceivers, who may wonder whether the behavior was motivated by a genuine internal commitment to egalitarianism or was externally motivated by desires to avoid appearing prejudiced to others. This article reports the development of a scale that measures perceptions of Whites' internal and external motives for avoiding prejudice (Perceived Internal Motivation Scale/Perceived External Motivation Scale [PIMS/PEMS]) and tests of its internal, test-retest, discriminant, convergent, and predictive validity among ethnic minority perceivers. Minorities perceived Whites as having internal and external motives for nonprejudiced behavior that were theoretically consistent with but distinct from established measures of minority-group members' concerns in interracial interactions. Tests of the predictive validity of PIMS/PEMS showed that when a White evaluator praised the mediocre essay of a minority target, minorities who were high PEMS and low PIMS were most likely to regard the feedback as inauthentic and derogate the quality of the essay.


1-Oxo-1H-phenalene-2,3-dicarbonitrile heteroaromatic scaffold: revised structure and mechanistic studies.
Synthesis of the originally proposed 8-oxo-8H-acenaphtho[1,2-b]pyrrol-9-carbonitrile led to a structural revision, and the product has now been identified as unknown compound 1-oxo-1H-phenalene-2,3-dicarbonitrile. The structural assignment was corroborated by detailed NMR studies and unambiguously confirmed by X-ray diffraction. A mechanism is proposed to explain the formation of this original heterocyclic scaffold. In addition, some new chemical transformations involving this compound are presented.


Gene expression profiling of ATP-binding cassette (ABC) transporters as a predictor of the pathologic response to neoadjuvant chemotherapy in breast cancer patients.
Drug resistance is a major obstacle to the successful chemotherapy. Several ATP-binding cassette (ABC) transporters including ABCB1, ABCC1 and ABCG2 have been known to be important mediators of chemoresistance. Using oligonucleotide microarrays (HG-U133 Plus 2.0; Affymetrix), we analyzed the ABC transporter gene expression profiles in breast cancer patients who underwent sequential weekly paclitaxel/FEC (5-fluorouracil, epirubicin and cyclophosphamide) neoadjuvant chemotherapy. We compared the ABC transporter expression profile between two classes of pretreatment tumor samples divided by the patients' pathological response to neoadjuvant chemotherapy (residual disease [RD] versus pathologic complete response [pCR]) ABCB3, ABCC7 and ABCF2 showed significantly high expression in the pCR. Several ABC transporters including ABCC5, ABCA12, ABCA1 ABCC13, ABCB6 and ABCC11 showed significantly increased expression in the RD (p<0.05). We evaluated the feasibility of developing a multigene predictor model of pathologic response to neoadjuvant chemotherapy using gene expression profiles of ABC transporters. The prediction error was evaluated by leave-one-out cross-validation (LOOCV). A multigene predictor model with the ABC transporters differentially expressed between the two classes (p<or=0.003) showed an average 92.8% of predictive accuracy (95% CI, 88.0-97.4%) with a 93.2% (95% CI, 85.2-100%) positive predictive value for pCR, a 93.6% (95% CI, 87.8-99.4%) negative predictive value, a sensitivity of 88.1%(95% CI, 76.8-99.4%), and a specificity of 95.9% (91.1% CI, 87.8-100%). Our results suggest that several ABC transporters in human breast cancer cells may affect the clinical response to neoadjuvant chemotherapy, and transcriptional profiling of these genes may be useful to predict the pathologic response to sequential weekly paclitaxel/FEC in breast cancer patients.


Net heterolytic cleavage of B-H and B-B bonds across the N-Pd bond in a cationic (PNP)Pd fragment.
The use of weakly coordinating anions BAr(F)(4) (where Ar(F) = 3,5-(CF(3))(2)C(6)H(3)) and CB(11)H(12) allows one to access clean reactions of the [(PNP)Pd](+) fragment (PNP = bis(2-(i)Pr(2)P4-Me-phenyl)amido) with the B-H bond in catecholborane (CatBH) and catecholdiboron (CatBBCat). In both cases, a net heterolytic cleavage of B-H or B-B takes place, with the nitrogen atom of PNP being a recipient of a boryl fragment. The resultant products [(PN(BCat)P)PdH](+) (2) and [(PN(BCat)P)PdBCat](+) (3) were isolated as either BAr(F)(4) or CB(11)H(12) salts and fully characterized. They are susceptible to hydrolysis, with the B-N bond hydrolyzing selectively and rapidly at RT to give [(PN(H)P)PdH](+) (1) and [(PN(H)P)PdBCat](+) (4). Notably, 4 and 2 are isomers, but they do not interconvert even under thermolysis at 90 °C. The Pd-B bond in 4 can be further hydrolyzed more slowly, to give 1. On the other hand, a Pd-B bond was formed from the Pd-H bond in 2 by reaction with excess CatBH (and evolution of H(2)), producing 3.


Female sexual arousal disorder: new insights.
Epidemiologic investigations of women with female sexual dysfunction (FSD) from well-designed, random-sample, community-based populations are limited. Based on available information, FSD is common and estimated to occur in 22-43% of women. There are limited data on age-related and para-aging risk factors, which are critical to understand when planning treatment and prevention efforts. Based on correlates of FSD, associated risk factors include age, education, history of sexual abuse or sexually transmitted disease, overall state general happiness and physical health. This brief overview attempts to review what is known about the female sexual anatomy, describes factors that may affect female sexual responsiveness, and identifies several areas where additional research is needed to promote understanding of this complex physiological and psychosocial phenomenon. International Journal of Impotence Research (2000) 12, Suppl 4, S152-S157.


Delayed akathisia and suicidal attempts following epidural droperidol infusion--a case report.
Epidural administration of droperidol has been used to prevent postoperative nausea and vomiting (PONV) caused by opioids, but the adverse reactions were relatively neglected. We present a patient who received patient-controlled epidural analgesia (PCEA) with bupivacaine-morphine-droperidol mixture for one and half days following hemorrhoidectomy, developed paroxysmal adverse reactions of akathisia, dysphoria, and suicidal attempts 3 days after the initiation of the treatment. The use of droperidol in PCEA for prevention of nausea and vomiting therefore needs to be re-evaluated according to the serious side effects occurring in our case.


[The cultural characteristics of keratinocytes from newborn rats].
Results of cultivation of newborn rat keratinocytes are presented, differences between growing rat and human keratinocytes in culture being revealed in addition to possibilities of experimental use of these results. It has been shown that a rat keratinocyte layer forms faster than a human one: the former it is thinner and contains twice less layers. The main peculiarity of rat keratinocytes in culture is their ability to grow successfully without feeder cells, while the presence of feeder cells is crucial for human keratinocyte growth in culture.


The uptake of horseradish peroxidase in monkey temporomandibular joint synovium after occlusal alteration.
We conducted an electron microscopic study on the alterations in the temporomandibular joint (TMJ) synovium of the monkey after it was subjected to unilateral bite-raising, by means of a maxillary occlusal splint. The uptake of intravenously injected horseradish peroxidase (HRP) by type A cells was demonstrated in the disturbed TMJ. The uptake of HRP decreased three to six wk after occlusal alteration, and was the same as in normal type A synovial cells after 16 wk.


2-amino-2-oxazolines as subtype selective alpha(2) adrenoceptor agonists.
Cyclohexylamino oxazoline 1 (AGN 190837), an analogue of 2 (Bay a6781), is a potent alpha(2) adrenoceptor agonist. On the basis of a design generated by receptor-ligand modeling, a number of cyclohexyl and norbornyl analogues were synthesized wherein the propyl group of 1 was replaced by phenylalkyl subsituents. This resulted in compound 6 being an alpha(2c) selective agonist, as well as 7 and 9 being alpha(2a)/alpha(2c) selective.


Universal equation of state and pseudogap in the two-dimensional Fermi gas.
We determine the thermodynamic properties and the spectral function for a homogeneous two-dimensional Fermi gas in the normal state using the Luttinger-Ward, or self-consistent T-matrix, approach. The density equation of state deviates strongly from that of the ideal Fermi gas even for moderate interactions, and our calculations suggest that temperature has a pronounced effect on the pressure in the crossover from weak to strong coupling, consistent with recent experiments. We also compute the superfluid transition temperature for a finite system in the crossover region. There is a pronounced pseudogap regime above the transition temperature: the spectral function shows a Bogoliubov-like dispersion with backbending, and the density of states is significantly suppressed near the chemical potential. The contact density at low temperatures increases with interaction and compares well with both experiment and zero-temperature Monte Carlo results.


Comparison between dexmedetomidine and midazolam for sedation of eclampsia patients in the intensive care unit.
This study compares the effectiveness of midazolam and dexmedetomidine for the sedation of eclampsia patients admitted to our intensive care unit (ICU). Forty women with eclampsia requiring termination of pregnancy by caesarean delivery were randomized in to 2 groups of 20 to receive either midazolam or dexmedetomidine. The midazolam group received a loading dose of 0.05 mg/kg followed by an infusion of 0.1 mg kg(-1) h(-1). The dexmedetomidine group loading dose was 1 microg/kg per 20 minutes, followed by continuous infusion at 0.7 microg kg(-1) h(-1). Heart rate, blood pressure, Ramsey sedation score, antihypertensive need, convulsion fits, and duration in ICU were monitored and recorded all through the ICU stay. Dexmedetomidine markedly reduced heart rates for the first 24 hours (P < .05) compared with midazolam, but there were no differences at 48 and 72 hours. Mean arterial blood pressures were similar in the 2 groups (P > .05), although in the dexmedetomidine group, it was lower at 5, 6, 12, and 24 hours compared with the first 4 hours (P < .05). Moreover, fewer patients given dexmedetomidine required nitroglycerine and nitroprusside (P < .05). The duration of ICU stay was less in the dexmedetomidine group, 45.5 hours (range, 15-118 hours), than in the midazolam group, 83 hours (minimum-maximum, 15-312 hours). Dexmedetomidine sedation in eclampsia patients is effective in reducing the demand for antihypertensive medicine and duration of ICU stay.


Suppression of host resistance to Listeria monocytogenes by acute cold/restraint stress: lack of direct IL-6 involvement.
We conducted kinetic studies to evaluate the effects of acute cold/restraint stress (ACRS) on both primary and secondary host resistance to Listeria monocytogenes (LM). The involvement of IL-6 also was investigated using IL-6 knockout (KO) mice on the BALB/c background. ACRS dramatically increased the serum corticosterone levels, indicating that ACRS activated the hypothalamic-pituitary-adrenal (HPA) axis. ACRS significantly inhibited host resistance to LM during a primary but not a secondary LM infection. During the primary infection, ACRS caused a significant delay in clearance of LM, loss of body weight, reduced food/water intake, and elevated levels of pro-inflammatory cytokines (IL-6, IL-1beta, and TNFalpha) and IFNgamma. ACRS IL-6 KO mice showed higher LM burdens than did IL-6 KO controls, suggesting that IL-6 is not required for the ACRS-impairment of host resistance. Elevated levels of IL-1beta and TNFalpha may compensate for the absence of IL-6 and maintain the ACRS-induced impairment, in that the serum and splenic IL-1beta and TNFalpha levels were significantly higher in infected ACRS IL-6 KO mice, but not in control IL-6 KO mice, as compared to respective wild type controls. ACRS appears to inhibit IL-6 independent mechanisms associated with innate immunity and/or the development of adaptive immunity, but these reactions are unable to modulate the more efficient secondary immune responses.


Plasticity of mouse brain docosahexaenoic acid: modulation by diet and age.
Decreases in brain docosahexaenoic acid (DHA) have been associated with losses in brain function leading to an interest in the conditions which lead to such brain decreases, and such variables as age. Also of relevance would be the rate of repletion of DHA when the n-3 dietary deficiency is reversed. This experiment describes dietary deficiency in n-3 fatty acids induced in weanling (3 week) and young adult (7 week) mice. There was an immediate and continuous loss of brain DHA with similar rates in the two age groups. Serum DHA declined more rapidly in younger animals with respect to similarly treated adults. Brain and serum docosapentaenoic acid (DPAn-6) increased more rapidly and to higher levels in the younger animals. A second experiment determined the rates of normalization of brain fatty acid profiles when alpha-linolenic acid was added to the diets of n-3 deficient mice. Brain DHA recovery occurred at a faster rate (half-time, T 1/2 = 1.4 weeks) when begun at weaning relative to young adult mice (T 1/2 = 3.5 weeks). Correspondingly, brain DPAn-6 recovered faster in the younger animals; the adult group had a half-time of more than twice that of the 3-week old group. This study therefore demonstrates that the young adult mouse brain DHA is somewhat plastic and can be partially depleted via a low n-3 fatty acid diet and subsequently restored when dietary n-3 fatty acids are repleted. Relevance of these findings for human nutrition is discussed.


Hepatic canalicular membrane transport of bile salt in C57L/J and AKR/J mice: implications for cholesterol gallstone formation.
C57L/J (gallstone-susceptible) and AKR/J (gallstone-resistant) mice have been utilized for quantitative trait loci (QTL) analysis to identify the Lith 1 locus for cholelithiasis. Abcb11 encodes for the liver canalicular membrane bile salt export pump (BSEP), which maps to this QTL and is a candidate gene for Lith 1. We investigated the transmembrane transport of taurocholate in canalicular liver membrane vesicles isolated from these murine strains. Canalicular liver plasma membranes (cLPM) and RNA were isolated from C57L/J and AKR/J mice livers, and were utilized for Northern and Western blot analysis and functional (3)H-taurocholate uptake studies. ATP-dependent (3)H-taurocholate uptake was significantly higher in AKR/J, compared to C57L/J mice. V(max) was 127 vs. 42 pmol TC/mg/s in the murine strains, respectively, while K(m) was unchanged. In contrast, gene and protein expression of hepatic Abcb11 was increased three-fold in C57L/J, compared to AKR/J mice. Thus, Abcb11 bile salt transport activity per unit protein was reduced nine-fold in the C57L/J, compared to AKR/J mice. In contrast, canalicular membrane cholesterol:phospholipid content was also significantly higher in the C57L/J mice. We conclude that gallstone-susceptible C57L/J mice demonstrate increased gene and canalicular membrane expression of Abcb11, however, taurocholate transport is functionally diminished. The latter may be due to the increased cholesterol membrane content of the cLPM in C57L/J mice. These findings may be important for the pathogenesis of gallstone formation.


Bridging biophysics and neurology: aberrant phase transitions in neurodegenerative disease.
Biomolecular condensation arising through phase transitions has emerged as an essential organizational strategy that governs many aspects of cell biology. In particular, the role of phase transitions in the assembly of large, complex ribonucleoprotein (RNP) granules has become appreciated as an important regulator of RNA metabolism. In parallel, genetic, histopathological and cell and molecular studies have provided evidence that disturbance of phase transitions is an important driver of neurological diseases, notably amyotrophic lateral sclerosis (ALS), but most likely also other diseases. Indeed, our growing knowledge of the biophysics underlying biological phase transitions suggests that this process offers a unifying mechanism to explain the numerous and diverse disturbances in RNA metabolism that have been observed in ALS and some related diseases - specifically, that these diseases are driven by disturbances in the material properties of RNP granules. Here, we review the evidence for this hypothesis, emphasizing the reciprocal roles in which disease-related protein and disease-related RNA can lead to disturbances in the material properties of RNP granules and consequent pathogenesis. Additionally, we review evidence that implicates aberrant phase transitions as a contributing factor to a larger set of neurodegenerative diseases, including frontotemporal dementia, certain repeat expansion diseases and Alzheimer disease.


Giant localized fibrous mesothelioma: an unusual large intrathoracic tumor.
Localized fibrous mesotheliomas are rare intrathoracic tumors arising from the pleural tissue. They are mostly benign tumors, with dimensions ranging from a small nodule to a large intrathoracic tumor. This paper describes the presence of giant localized fibrous mesothelioma filling the lower left pleural cavity, which developed over a 20-year period. Surgical resection of the tumor showed a large, localized fibrous mesothelioma 14 cm in diameter. The clinical manifestations of localized fibrous mesotheliomas are very variable. Small tumors may be asymptotic, while large tumors may cause respiratory, cardiac or metabolic symptoms. Complete surgical resection is the preferred treatment and is usually curative. Careful follow-up is indicated because recurrence may occur, even many years after the initial operation.


Noise correction for the exact determination of apparent diffusion coefficients at low SNR.
Noise in MR image data increases the mean signal intensity of image regions due to the usually performed magnitude reconstruction. Diffusion-weighted imaging (DWI) is especially affected by high noise levels for several reasons, and a decreasing SNR at increasing diffusion weighting causes systematic errors when calculating apparent diffusion coefficients (ADCs). Two different methods are presented to correct biased signal intensities due to the presence of complex noise: 1) with Gaussian intensity distribution, and 2) with arbitrary intensity distribution. The performance of the correction schemes is demonstrated by numerical simulations and DWI measurements on two different MR systems with different noise characteristics. These experiments show that noise significantly influences the determination of ADCs. Applying the proposed correction schemes reduced the bias of the determined ADC to less than 10% of the bias without correction. Magn Reson Med 45:448-453, 2001.


Efficacy of monotherapy compared with combined antianginal drugs in the treatment of chronic stable angina pectoris: a meta-analysis.
To determine the relative efficacy of antianginal drugs administered as monotherapy or in combination in patients with chronic stable angina. A meta-analysis was performed on randomized trials, published in English between 1980 and 1999, that directly compared combined treatment and monotherapy. Twenty-two articles were included, all on the comparison of -blocker monotherapies to their combination with a calcium antagonist and 10 on the comparison of calcium antagonist monotherapies to their combination with a -blocker. Time to 1 mm ST-segment depression, total exercise duration and time to onset of anginal pain were significantly increased with the combined therapy compared to -blocker alone (by 8, 5 and 12%, respectively). Only time to 1 mm ST-segment depression was significantly increased with the combined therapy compared to calcium antagonist alone (by 9%). For all these parameters, the adjusted differences were significant only within 6 h following drug intake and were not significant after 6 h. No analysis of safety data could be performed. As far as exercise testing is concerned, the combination of a calcium antagonist and a -blocker is statistically more effective than either monotherapy. Further studies are needed to confirm the higher efficacy after the first 6 h following drug intake.


Pursuing justice in an era of managed care. Seattle-based system makes room for the underserved and uninsured.
The Sisters of Providence Health System (SPHS), based in Seattle, is dedicated to the search for justice. In 1983 the system's leaders decided to create SPHS-owned and -operated managed care plans for residents of the Pacific Northwest because they saw such plans as both the best way to rationalize the region's healthcare delivery and an opportunity to serve its poor and underserved. In Oregon, where the legislature passed the Oregon Health Plan in 1989, 21,000 persons are covered by Providence Health Plans; another 15,000 receive care through SPHS providers and networks. In Washington, whose Basic Health Plan enables customers to purchase coverage through payments adjusted to family sizes and incomes, 13,600 persons are enrolled in the version offered by SPHS; another SPHS plan covers 20,000 beneficiaries of the state's Aid to Families with Dependent Children program; in addition 18,600 elderly Washingtonians are enrolled in an SPHS-sponsored Medicare supplement program. SPHS has found that ownership of its plans enables it to integrate mission and business. But ownership also carries certain challenges. SPHS must, for instance, compete with for-profit organizations without compromising its core values. It must carefully coordinate the insurer and provider parts of its organization. And it must train all its employees in Catholic values and insist that its leaders create and enhance an ethical corporate culture.


Long-term suicide risk in schizophrenia spectrum psychoses: survival analysis by gender.
Patients with schizophrenia spectrum psychoses have a high risk of suicide. Suicide is more frequent in men. Our objective in this study was to investigate the long term suicide risk in schizophrenia spectrum psychoses in relation to gender. A cohort from 1973 to 1987 of 385 schizophrenia spectrum psychoses inpatients in Stockholm were followed up for cause of death in 2006. Twenty-six suicides (6.8%) occurred during the follow up of 24.4 years. There was no significant difference in suicide mortality between men (6.5%) and women (6.9%). There was no gender difference in death from other causes. These results indicate that patients with schizophrenia spectrum psychoses have a high long term suicide risk in both men and women. The high suicide risk in female patients deserves further research attention.


Use of Music Therapy to Improve Cognition in Older Adults With Dementia: An Integrative Review.
Dementia is considered a public health priority due to physical, psychological, economic, and social repercussions in older adults, their families, and caregivers. To address this issue, healthcare providers can use music therapy as a complementary therapy. This manuscript was elaborated to analyze and synthesize the current evidence of the use of music therapy to improve cognition in older adults with dementia. Using the Whittemore and Knafl (2005) method, databases searched were PubMed, CINAHL, Ovid, EBSCO, ProQuest, and PsycINFO, using the terms such as "Music Therapy," "Acoustic Stimulation," "Music," "Cognition," "Memory," "Attention," "Aged," and "Dementia." Studies that met the eligibility criteria were screened by title, abstract and full text. Quality of the studies were evaluated using critical appraisal tools and Cochrane "Risk of Bias" tool. A total of 211 articles were screened by title and abstract, but only 28 articles met the inclusion criteria and were full text screened. Of the 28 articles, only five studies were analyzed and synthesized as they focused specifically on music therapy and cognition. Three of the studies showed that active and active-passive approaches of music therapy produce significant effect on cognition in older adults with dementia. The common characteristic was the participation of music therapists or music teachers who delivered the music therapy sessions that resulted in improved cognition. As a safe, inexpensive intervention, it should be considered as a complementary therapy to positively impact cognition in older adults with different types of dementia and levels of severity.


Reproducibility of sputum smear examination for acid-fast bacilli: practical problems met during cross-checking.
A TB control programme in Bangladesh with proficiency testing of sputum smears for acid-fast bacilli (AFB) using cross-checking of routine smears. To document factors that may adversely affect repeatability of the AFB smear, and which should be taken into account for interpretation of cross-checking. A number of simple experiments falling within the scope of small routine laboratories in a developing country. Fuchsin staining is not stable, fading quickly in direct sunlight and combinations of high temperature and humidity. Diffuse daylight, immersion oil or xylene did not have the same effect. Contamination of smears by saprophytic mycobacteria may occur during staining or rinsing, with contaminants becoming visible only after restaining and cross-checking. Finally, AFB may be dislodged from smears during soaking in xylene or restaining, especially if the smears are made from thin, liquefied sputum. These possible interfering factors should be taken into account when organizing proficiency testing and interpreting its results.


Echocardiographic Assessment of Left Ventricular Systolic Function: An Overview of Contemporary Techniques, Including Speckle-Tracking Echocardiography.
Assessment of left ventricular systolic function has a central role in the evaluation of cardiac disease. Accurate assessment is essential to guide management and prognosis. Numerous echocardiographic techniques are used in the assessment, each with its own advantages and disadvantages. This review is based on a literature search of the PubMed, MEDLINE, EMBASE, and Scopus databases from inception through December 30, 2017, using the terms strain echocardiography, tissue Doppler strain, and speckle-tracking echocardiography. We provide the internist with a contemporary overview of current echocardiographic techniques used in the evaluation of left ventricular systolic function. In particular, we focus on the role of speckle-tracking echocardiography, including its utility in the detection of subclinical left ventricular dysfunction and the associated prognostic implications.


X-ray microanalysis and ultrastructural localization of cisplatin in liver and kidney of the rat.
Cisplatin or cis-diamminedichloroplatinum(II) is a platinum coordination compound showing clinically useful antitumor activity, but the major dose-limiting factor is a dose-dependent cumulative nephrotoxicity. At the electron microscopic level, platinum has been localized in the nucleus, microsomes and cytoplasm of cells of the kidney and liver in rats. This report confirms the subcellular localization of platinum and adds one more site of platinum accumulation, the microbody, based on results obtained with an energy-dispersive X-ray microanalyzer (EDX). After daily administration of cisplatin (0.5 mg/ml/kg body weight) successively for 5 weeks, accumulated platinum was detected in microbodies of hepatocytes and epithelial cells of proximal convoluted tubules of the rat. The major site of metal deposition in the kidney was the matrix of many microbodies in the epithelial cells of proximal convoluted tubules. EDX revealed the presence of platinum in those metallic deposits. The matrix of the nucleus also had metallic deposits but they were rather diffuse and platinum could not readily be detected on individual grains in the nucleus. In the liver, major damage was concentrated in hepatocytes, and other types of cells such as Kupffer cells, Ito cells and endothelial cells of capillaries were less affected. Metallic fine grains were localized in the cisterna of smooth-surfaced endoplasmic reticulum and in the matrix of microbodies. The nucleus of hepatocytes had few, if any, metallic precipitates. A specific type of metallic deposition was round aggregations of dense tubules in which platinum was detected by EDX. There was no evidence of platinum precipitation in mitochondria or Golgi complex. These findings suggest that the microbody may play an important role in degradation of the platinum complex both in hepatocytes and epithelial cells of proximal convoluted tubules.


Anisotropy of dynamic acoustoelasticity in limestone, influence of conditioning, and comparison with nonlinear resonance spectroscopy.
Anisotropy of wave velocity and attenuation induced by a dynamic uniaxial strain is investigated by dynamic acoustoelastic testing in limestone. Nonlinear resonance spectroscopy is performed simultaneously for comparison. A compressional resonance of the sample at 6.8 kHz is excited to produce a dynamic strain with an amplitude varied from 10(-7) to 10(-5). A sequence of ultrasound pulses tracks variations in ultrasonic velocity and attenuation. Variations measured when the ultrasound pulses propagate in the direction of the uniaxial strain are 10 times larger than when the ultrasound propagation occurs perpendicularly. Variations consist of a "fast" variation at 6.8 kHz and an offset. Acoustically induced conditioning is found to reduce wave velocity and enhance attenuation (offset). It also modifies "fast" nonlinear elastodynamics, i.e., wave amplitude dependencies of ultrasonic velocity and attenuation. At the onset of conditioning and beyond, different excitation amplitudes bring the material to non-equilibrium states. After conversion of velocity-strain dynamic relations into elastic modulus-strain dynamic relations and integration with respect to strain, the dynamic stress-strain relation is obtained. Analysis of stress-strain hysteresis shows that hysteretic nonlinear elasticity is not a significant source of the amplitude-dependent dissipation measured by nonlinear resonance spectroscopy. Mechanisms causing conditioning are likely producing amplitude-dependent dissipation as well.


Leptin and Adiponectin Serum Levels from Infancy to School Age: Factors Influencing Tracking.
Early adiponectin and leptin in children correlate with those measured at a later age. Prenatal and early life factors may influence the pattern of leptin and adiponectin longitudinal changes. We aimed to identify subgroups of children with distinct trajectories of leptin and adiponectin over the first eight years of life, and to explore determinants predisposing an individual to be included in a specific trajectory class. The analysis was based on data obtained from the EU Childhood Obesity Project (CHOP) cohort. The current study involved 459 children with adiponectin and leptin measured at 6 months, 5½ and 8 years of age. Three groups of leptin trajectories were identified: low-decreasing, medium-stable, and high-increasing, and two trajectory groups for adiponectin: lower and higher. The risk to be classified in the high-increasing group was higher than in the low-decreasing group for female gender (OR 10.67; 95% CI 4.94-23.05; p < 0.001); formula feeding (OR 3.34; 95% CI 1.11-10.09; p < 0.05); maternal overweight (OR 4.43; 95% CI 2.20-8.94; p < 0.001); and smoking in pregnancy (OR 4.14; 95% CI 2.07-8.29; p < 0.001). No predictors for being in the higher vs. lower adiponectin group were discovered. Mothers' smoking during pregnancy, maternal overweight, and formula feeding distinguished different courses of leptin trajectories; but the effect may be associated with changes in adiposity.


11C-hydroxytryptophan uptake and metabolism in endocrine and exocrine pancreas.
Determination of the residual β-cell mass using noninvasive tools might help to follow up the efficacy of new treatments in both type 1 (insulin-dependent) and type 2 (non-insulin-dependent) diabetes mellitus, including islet transplantation. β-cells are neuroendocrine cells that can take up and metabolize the serotonin precursor 5-hydroxytryptophan. The serotonin pathway may therefore be an attractive target for the development of an imaging tracer for residual β-cell mass. The aim of this study was to evaluate the uptake mechanism and the retention of the PET tracer (11)C-hydroxytryptophan in endocrine and exocrine pancreas in vitro and in vivo. The exocrine human pancreas carcinoma cell line (PANC-1) and the endocrine human insulinoma cell line (CM) were applied for in vitro (11)C-hydroxytryptophan accumulation/efflux experiments and blocking studies using inhibitors of key enzymes and transporters involved in the serotonin pathway. Animal experiments were performed on normal Wistar rats and on rats pretreated with the monoamine oxidase (MAO) inhibitor clorgyline. After intravenous injection of (11)C-hydroxytryptophan, a 60-min dynamic PET scan was acquired followed by an ex vivo biodistribution study. Autoradiography and hematoxylin-eosin staining were performed on the dissected pancreas to localize the radioactivity within the pancreatic tissue. (11)C-hydroxytryptophan accumulated rapidly in both endocrine CM cells and exocrine PANC-1 cells. In the exocrine cells, a rapid efflux of radioactivity was observed, whereas most radioactivity remained trapped in the endocrine cells. PET images showed clear accumulation of (11)C-hydroxytryptophan in the pancreas in both animal groups, but with a significant 3-fold higher retention of the radiopharmaceutical in clorgyline-treated animals. Ex vivo biodistribution studies confirmed the results obtained by PET. Autoradiographs did not discriminate between the exocrine and endocrine pancreas in control animals, whereas autoradiographs showed intense radioactive spots colocalized with the islets of Langerhans in clorgyline-treated animals. (11)C-hydroxytryptophan is trapped in β-cells but not in exocrine pancreatic cells. β-cell selectivity can be strongly enhanced by inhibition of MAO-A. This observation offers perspectives for the development of a more selective PET tracer for β-cell mass, based on an (11)C-hydroxytryptophan derivative with increased resistance toward degradation by MAO-A.


Synthesis and cytotoxicity studies of novel [1,2,4]triazolo[1,5-a]pyrimidine-7-amines.
A series of novel N-anilino-5-methyl-2-(3-(5-(alkylaminomethyl)furan-2-yl-methylthio)propyl)-[1,2,4]triazolo-[1,5-a]pyrimidine-7-amine derivatives were synthesized and evaluated for their in vitro cytotoxicity against two cancer cell lines, Bel-7402 and HT-1080. Compounds 9, 14, 19 and 23 possessed marked cytotoxicity, especially 23 (with IC(50) values of 15.0 microM and 7.8 microM against Bel-7402 and HT-1080 cell lines, respectively), which had emerged as lead compound. The activity was found to depend strongly on substitution pattern of the side chains at C-2 position, and 4-triflouromethylanilino substituent at C-7 position was an option for anticancer potency.


Stimulation of cyclic GMP accumulation by sodium nitroprusside is potentiated via a Gs mechanism in intact pinealocytes.
Cyclic GMP accumulation in pinealocytes is elevated > 100-fold by norepinephrine (NE) through a mechanism involving conjoint activation of alpha 1- and beta 1-adrenergic receptors. Little or no stimulation occurs if either alpha 1- or beta 1-adrenergic receptors alone are activated. It appears that alpha 1-adrenergic effects are mediated by Ca2+ acting in part through nitric oxide (NO), and beta 1-adrenergic effects are mediated by Gs. In the study presented here we investigated effects of adrenergic agonists or related postreceptor-active agents on stimulation of pineal cyclic GMP accumulation by the NO generator sodium nitroprusside (NP). The cyclic GMP response to NP (1 mM) was potentiated by NE and isoproterenol (ISO) but not by phenylephrine, indicating that activation of beta 1-adrenergic receptors potentiates the effects of NP. Similarly, vasoactive intestinal peptide (VIP), cholera toxin (CTX), and forskolin, all of which are known to mimic the effects of ISO in this system, also potentiated the effects of NP. In contrast, neither dibutyryl cyclic AMP nor agents that elevate intracellular Ca2+ levels caused marked potentiation of the effects of NP on pineal cyclic GMP. Depletion (90%) of Gs alpha by 21-h treatment with CTX reduced beta-adrenergic potentiation of NP. These findings indicate that beta-adrenergic agonists and VIP potentiate the effects of NP through a mechanism involving Gs. The molecular basis of this action may be an increase in guanylyl cyclase responsiveness to NO.


Internalization of the lymphocytic surface protein CD22 is controlled by a novel membrane proximal cytoplasmic motif.
CD22 is a key receptor on B-lymphocytes that modulates signaling during antigenic stimulation. We have defined a novel cytoplasmic motif in human CD22 that controls its unusually rapid turnover at the plasma membrane. Chimeric and mutated CD22alpha cDNA vectors were constructed and stably transfected in CD22-negative Jurkat T-lymphocytic cells. Two assays were employed to measure CD22alpha internalization: first, cytoplasmic uptake of radioiodinated anti-CD22 monoclonal antibody; and second, lethal targeting of a toxin, saporin, into cells via CD22 using bispecific F(ab')2 ([anti-CD22 x anti-saporin]) antibody. Results showed that CD22alpha lacking a cytoplasmic tail was not internalized and that replacement of the cytoplasmic tail of CD19 with that of CD22alpha resulted in a chimeric molecule that behaved like CD22alpha and internalized rapidly. Step-wise deletion of the cytoplasmic tail of CD22alpha located the internalization motif to a polar region of 11 residues (QRRWKRTQSQQ) proximal to the plasma membrane, a part of the molecule predicted to form a coil or turn structure. Interestingly, additional CD22 mutants showed that the two glutamine residues sandwiching the serine are critical to internalization but that the serine itself is not.


Upregulation of vasopressin V2 and aquaporin 2 in the inner medullary collecting duct of cardiomyopathic hamsters is attenuated by enalapril treatment.
Previous studies showed that aquaporin 2 (AQP2) is elevated in the kidney of the heart failure rat suggesting that an increased amount of AQP2 contributes to water retention in heart failure. We performed the present study to determine whether angiotensin II play a role in causing an increase in the expression of arginine vasopressin (AVP) V2 and AQP2 mRNA in the kidney of the cardiomyopathic hamster. The expression of AVP V2 and AQP2 mRNA in the inner medullary collecting duct (IMCD) was measured by competitive reverse transcriptase-polymerase chain reaction (RT-PCR) before and after treatment with an angiotensin-converting enzyme inhibitor, enalapril. Our results showed that the expression of AVP V2 (0.53 +/- 0.05 v 1.03 +/- 0.15 amol/microg of total RNA, P <.01) and AQP2 mRNA (0.027 +/- 0.002 v 0.036 +/- 0.002 amol/microg of total RNA, P <.05) in the IMCD of the cardiomyopathic hamster is upregulated. Treating the cardiomyopathic hamster with enalapril for 7 days negated the changes. In situ hybridization experiments confirmed the intensity of the signals for both AVP V2 and AQP2 mRNA was more intense in the IMCD of the cardiomyopathic hamster. Enalapril treatment reduced the signal intensity to a level comparable to the normal hamster. These results suggested that the increases in the expression of AVP V2 and AQP2 mRNA are mediated by angiotensin II.


Beta-selective arabinofuranosylation using a 2,3-O-xylylene-protected donor.
Reported is a novel stereoselective beta-arabinofuranosylation that makes use of a conformationally restricted 2,3-O-xylylene-protected arabinofuranosyl donor. Optimization of the reaction conditions showed that factors including the structure of the acceptor alcohol, substrate concentration, and protecting group on O-5 of the donor affect the stereochemical outcome of the glycosylation. To demonstrate the utility of the methodology, the synthesis of an oligosaccharide fragment from the mycobacterial cell wall polysaccharide lipoarabinomannan was carried out.


Change in semen quality and sperm chromatin structure following occupational styrene exposure. ASCLEPIOS.
Organic solvents have been suspected to exert detrimental effects on human spermiogenesis. Styrene, which is both mutagenic and neurotoxic, was selected as a suitable organic solvent for further assessment of a possible effect on semen quality and sperm DNA damage. Semen samples were collected from 23 reinforced plastics workers at the time of employment and after 6 months of styrene exposure and from 21 nonexposed farmers. Intra-individual changes in conventional semen parameters and sperm-DNA denaturation patterns were related to the internal dose of styrene exposure as measured by postshift urinary mandelic acid. A statistically significant decline in sperm density was seen during styrene exposure from 63.5 to 46.0 million sperm/ml, whereas no decline was seen in the nonexposed subjects. The total sperm count was almost halved from an initial value of 175 million sperm/ejaculate. However, no relationship was apparent when the sperm parameters were related to internal levels of exposure. However, an exposure-response relationship was shown for DNA-denaturation patterns, but the numbers were small. A declining sperm count following styrene exposure is suggested. However, the findings of the internal and external comparisons are inconsistent, and this may be due to the high intraindividual variability of semen parameters and the limited study size but may also be attributable to a weak internal exposure gradient. Spermatogenesis may be vulnerable to styrene exposure. However, due to the small numbers these findings are only preliminary.


Circadian disruption and biomarkers of tumor progression in breast cancer patients awaiting surgery.
Psychological distress, which can begin with cancer diagnosis and continue with treatment, is linked with circadian and endocrine disruption. In turn, circadian/endocrine factors are potent modulators of cancer progression. We hypothesized that circadian rest-activity rhythm disruption, distress, and diurnal cortisol rhythms would be associated with biomarkers of tumor progression in the peripheral blood of women awaiting breast cancer surgery. Breast cancer patients (n=43) provided actigraphic data on rest-activity rhythm, cancer-specific distress (IES, POMS), saliva samples for assessment of diurnal cortisol rhythm, cortisol awakening response (CAR), and diurnal mean. Ten potential markers of tumor progression were quantified in serum samples and grouped by exploratory factor analysis. Analyses yielded three factors, which appear to include biomarkers reflecting different aspects of tumor progression. Elevated factor scores indicate both high levels and strong clustering among serum signals. Factor 1 included VEGF, MMP-9, and TGF-β; suggesting tumor invasion/immunosuppression. Factor 2 included IL-1β, TNF-α, IL-6R, MCP-1; suggesting inflammation/chemotaxis. Factor 3 included IL-6, IL-12, IFN-γ; suggesting inflammation/TH1-type immunity. Hierarchical regressions adjusting age, stage and socioeconomic status examined associations of circadian, distress, and endocrine variables with these three factor scores. Patients with poor circadian coordination as measured by rest-activity rhythms had higher Factor 1 scores (R(2)=.160, p=.038). Patients with elevated CAR also had higher Factor 1 scores (R(2)=.293, p=.020). These relationships appeared to be driven largely by VEGF concentrations. Distress was not related to tumor-relevant biomarkers, and no other significant relationships emerged. Women with strong circadian activity rhythms showed less evidence of tumor promotion and/or progression as indicated by peripheral blood biomarkers. The study was not equipped to discern the cause of these associations. Circadian/endocrine aberrations may be a manifestation of systemic effects of aggressive tumors. Alternatively, these results raise the possibility that, among patients with active breast tumors, disruption of circadian activity rhythms and elevated CAR may facilitate tumor promotion and progression.


[Bifurcation resection of the left mainstem bronchus and segmentectomy for double granular cell tumors].
The authors report a case of a 57-year old asymptomatic patient, whose routine chest X-ray demonstrated a left-sided lung tumour. Bronchoscopy, chest CT and PET-CT revealed double granular cell tumours on the posterior wall of the distal part of the left mainstem bronchus as well as in the bronchus of the segment 6, in addition to the suspected malignant tumour in the 2nd segment. His surgical management involved the atypical resection of segment 2 lesion first, which was tuberculotic origin based on frozen section. Next, the double granular cell tumours were removed by segmentectomy of segment 6 and bifurcation resection of the mainstem bronchus. In case of granular cell tumours, resection of the mainstem bronchus is a safe procedure with good results. Further, surgical exploration is indicated in symptomatic patients with a suspicion of malignant coin lesions.


Endocavitary contrast enhanced ultrasound (CEUS)--work in progress.
To demonstrate the benefit concerning localisation, measurement and visualisation of complications of drained fluid collections in the abdomen by applying ultrasound contrast agent via drainage catheters. In addition, to investigate the usefulness of CEUS in applying the agents in the biliary tract or when given orally. A single drop of SonoVue® was added to 0.9 % saline solution and instilled via drainage catheters. Location, dimensions and complications of drained fluid collections were recorded and compared to the results of sonographic examination using saline solution alone and fluoroscopic examination using iodinated contrast agents. The biliary system was visualised by applying the solution via nasobiliary drains or via ERC catheterisation. Orally administered solutions consisted of one drop of SonoVue® in 50 ml aqua. Admixture of an ultrasound contrast agent to saline solution facilitates position monitoring of the drains in fluid collections and provides reliable information on the dimensions of the drained collection. Complications like fistulae to the biliary system, blood vessels, small or large intestine or to the peritoneal cavity are precisely displayed. The biliary system is shown in detailed description. Orally administered, the contrast agent is visible after intake long unto the colon. Insufficient anastomoses or spontaneous perforations become detectable. The application of ultrasound contrast agents via drainage catheters provides substantial information on location and dimensions of drained fluid collections and their communication with surrounding organ structures. The biliary system can be visualised. Oral administration is feasible and provides important additional information.


Anatomic guidelines for augmentation of the cheek and infraorbital hollow.
Mid-face reflation requires a sophisticated knowledge of bony and soft tissue anatomy. To blend knowledge of the relevant anatomy with clinical experience to generate procedural guidelines for reproducible volumization of the midface. A demonstration of cadaver head dissection was followed by injection of colored hyaluronic acid and calcium hydroxylapatite fillers into cadaver heads in the anatomy laboratory. The injected cadaver heads were then dissected to assess the anatomical position of the injected fillers. Live patient injections followed using the anatomic learning. Best practice guidelines for midface and infraorbital hollow injections were discussed. Aesthetic augmentation of the midface requires knowledge of the properties of each filler and of the underlying anatomy, as well as an understanding and documentation of the subject's aesthetic concerns.


The measurement of stenosis of the internal carotid artery: comparison of doppler ultrasound, digital subtraction angiography and the 3D CT volume rendering technique.
To determine the variability of measurement of stenosis of the internal carotid artery (ICA) using Doppler ultrasound, digital subtraction angiography (DSA) and the three-dimensional volume rendering technique (3D CT) in the high-grade stenosis band (70-100%). A prospective study of preoperative findings in 64 patients. Doppler ICA stenosis was assessed according to combined Doppler acoustic standard criteria (CDASC) and peak systolic velocity (PSV). DSA and 3D CT stenosis were measured using the NASCET method. The results were compared using kappa statistics and Pearson's correlation coefficient. Agreement on the degree of ICA stenosis was statistically very good for DSA and 3D CT (kappa = 0.81, CI 0.69-0.93): Pearson's correlation coefficient was 0.88 (CI 0.76-0.90). The comparison of Doppler ultrasound with DSA showed good agreement (kappa 0.70, CI 0.58-0.82): Pearson's correlation coefficient was 0.61 (CI 0.43-0.74). The disagreement rate on occlusion was 3% between DSA and 3D CT and was rather high (10.9%) between Doppler ultrasound and DSA. The clinical decision to operate on an ICA stenosis will be strongly influenced by the diagnostic method used. DSA and 3D CT correlate well, whereas Doppler ultrasound tends to differ at the high end of the high-grade stenosis band (90% occlusion), underestimating (compared with DSA) the degree of stenosis.


Vascular architecture in free flaps: Analysis of vessel morphology and morphometry in murine free flaps.
The aim of this study was to analyze the development of vascular architecture as well as vascular morphometry and morphology of anastomosed microvascular free flaps. Free pectoral skin flaps were raised in 25 rats and anastomosed to the femoral vessels in the groin region. CD31 immunohistology was performed after 3, 7 and 12 d (each 5 animals each) to analyze microvessel density (MVD), microvessel area (MVA) and microvessel size (MVS). Microvascular corrosion casting was performed after 7 and 12 d (5 animals each) to analyze vessel diameter (VD), intervascular distance (IVD), interbranching distance (IBD), and branching angle (BA). Further on, sprout and pillar density as hallmarks of sprouting and intussusceptive angiogenesis were analyzed. Pectoral skin isles from the contralateral side served as controls. A significantly increased MVD was found after 7 and 12 d (p each <0.001). MVA was significantly increased after 3, 7 and 12 d (p each <0.001) and a significantly increased MVS was analyzed after 3 and 7 d (p each <0.001). VD and IVD were significantly increased after 7 and 12 d (p each <0.001). For IBD, a significantly increase was measured after 7 d (p < 0.001). For IBA, sprout and pillar density, no significant differences were found (p each ≥0.05). Significant changes in the vascular architecture of free flaps after successful microvascular anastomosis were seen. Since there was no evidence for sprout and pillar formation within the free flaps, the increased MVD and flap revascularization might be induced by the receiving site.


Identification of a functional apolipoprotein E promoter polymorphism regulating plasma apolipoprotein E concentration.
There is compelling evidence that the plasma apolipoprotein E (APOE) concentration, in addition to the APOE ε2/ε3/ε4 genotype, influences plasma lipoprotein levels, but the functional genetic variants influencing the plasma APOE concentration have not been identified. Genome-wide association studies in 2 cohorts of healthy, middle-aged subjects identified the APOE locus as the only genetic locus showing robust associations with the plasma APOE concentration. Fine-mapping of the APOE locus confirmed that the rs7412 ε2-allele is the primary genetic variant responsible for the relationship with plasma APOE concentration. Further mapping of the APOE locus uncovered that rs769446 (-427T/C) in the APOE promoter is independently associated with the plasma APOE concentration. Expression studies in 199 human liver samples demonstrated that the rs769446 C-allele is associated with increased APOE mRNA levels (P=0.015). Transient transfection studies and electrophoretic mobility shift assays in human hepatoma HepG2 cells corroborated the role of rs769446 in transcriptional regulation of APOE. However, no relationships were found between rs769446 genotype and plasma lipoprotein levels in 2 cohorts (n=1648 and n=1039) of healthy middle-aged carriers of the APOE ε3/ε3 genotype. rs769446 is a functional polymorphism involved in the regulation of the plasma APOE concentration.


Regional cerebral blood flow in Alzheimer's disease: comparison between short and long-term donepezil therapy.
Treatment with donepezil improves cognitive function of patients with Alzheimer's disease (AD) when compared to a placebo-controlled group. The purpose of this study was to investigate changes in regional cerebral blood flow (rCBF) of AD patients in short-term and long-term treatment with donepezil. rCBF was measured by N-isopropyl-p-123I-iodoamphetamine (IMP) autoradiography method. CBF measurements were performed in 17 AD patients before treatment and after 3 months (short-term therapy) and 1 year (long-term therapy). Regions of interest were set at cerebral cortex and cerebellar hemisphere. We used absolute CBF and relative CBF expressed as ratio to cerebellar CBF. Significant increases in relative rCBF were noted in the frontal, parietal and temporal lobes at the end of short-term therapy. rCBF was decreased after the long-term therapy, whereas rCBF was still increased to a slight extent, as compared with the pre-treatment levels. Absolute rCBF showed minimal change and a tendency to decline. Relative rCBF significantly increased in the short-term donepezil therapy, while following the long-term therapy, rCBF decreased to the pre-treatment level.


Long-term treatment of farnesyltransferase inhibitor FTI-277 induces neurotoxicity of hippocampal neurons from rat embryo in a ROS-dependent manner.
Despite the well established anti-cancer effect of farnesyltransferase inhibitor FTI-277, the neurotoxic effects of the agent are not yet clearly defined at the molecular and cellular levels. Here, we report the neurotoxic effects of FTI-277 and the involvement of reactive oxygen species (ROS) in FTI-induced neurotoxicity. Although there is no significant effect of FTI-277 for 2 days, long-term treatment of FTI-277 for 4 days induced dramatic reduction in outgrowth, maturation and branching of neuritis and considerable cytoxicity in a dose- and time-dependent manner in primary cultured rat embryo hippocampal neurons. Interestingly, FTI-277 for 4 days dramatically decreased expression of synapsin I, a crucial molecule involved in the neuronal growth and plasticity, and increased a cytotoxic G-protein RhoB of which ectopic expression induced the neurotoxicity in hippocampal neurons. Moreover, treatment with FTI-277 dramatically increased intracellular levels of ROS, which was sustained for 4 days; while blockage of ROS rescued FTI-277-induced neurotoxicity as well as both decrease of synapsin I and increase of RhoB. Taken together, these results provide the molecular insights for the mechanisms which might be of use aiming for avoiding neurotoxic side effects by FTI agent for a drug development for a clinical use.


A longitudinal study of the effects of early abuse on later victimization among high-risk adolescents.
Although previous research on adolescents finds a link between early abuse and later victimization, the majority of this research is cross-sectional and based on samples of currently homeless adolescents. Therefore, factors that predict the likelihood of victimization have not been systematically examined. As such, the current study longitudinally examines the effects of early abuse and poor parenting on victimization via running away, delinquency, and early sexual onset among a sample of over 700 currently housed high-risk adolescents. Results revealed that having experienced sexual and physical abuse, as well as lower levels of parental monitoring and closeness, significantly predicted running away at wave 1. Adolescents who had run at wave 1 were significantly more likely to run again, more likely to engage in delinquency, and more likely to have had an early sexual onset at wave 3, all of which significantly predicted victimization at wave 4.


Physician behaviors, patient perceptions, and patient characteristics as predictors of satisfaction of hospitalized adult cancer patients.
To examine potential predictors of cancer patient satisfaction with physician behavior, 366 cases were studied. Physician behavior was measured on morning rounds using the Physician Behavior Check List (PBCL). Patient satisfaction and perceptions were assessed after the visit. Patient characteristics were obtained from the chart and the physician. Results showed wide variation in physician behavior; no "standard" set of behaviors was seen in all interactions. Patient satisfaction was high (mean = 87.8 mm on a 100-mm scale). Path analysis showed four variables predicted 62% of the variance in patient satisfaction. The strongest predictor was the patient perception item, "perception of needs addressed that day." Other predictors were perception of emotional support provided by the physician, age (older), and one physician behavior, "discusses treatment." Patient perceptions of needs met or emotional support provided were predicted by perceptions of the occurrence of physician behaviors involving information such as the diagnosis and tests and treatment. Overall, patient perceptions of physician behaviors were stronger predictors of patient satisfaction than the actual occurrence or absence of those behaviors.


Phase behavior of mixed phosphatidylglycerol/phosphatidylcholine multilamellar and unilamellar vesicles.
The phase behavior of dipentadecanoylphosphatidylglycerol (DC15PG)/dimyristoylphosphatidylcholine (DMPC) mixtures has been studied in both small, unilamellar vesicles and large, multilamellar vesicles. We have used both the steady-state fluorescence polarization of 1,6-diphenyl-1,3,5-hexatriene (DPH) and high-sensitivity differential scanning calorimetry to detect temperature-dependent changes in membrane structure. Electron microscopy has demonstrated different fracture face morphologies for large, multilamellar vesicles depending on sample composition and temperature. These data have been interpreted in terms of proposed phase diagrams for this lipid mixture. The shapes of the proposed phase diagrams have led us to conclude that DMPC and DC15PG mix freely in the plane of a lipid bilayer only at less than 50 mol % DC15PG. At higher DC15PG content, the data have been interpreted as reflecting substantial compositional inhomogeneities in the plane of the bilayer, if not phase immiscibility, even in the fluid phase. In addition, small vesicles containing greater than 50 mol % DC15PG were unstable in the ordered phase and spontaneously converted to larger vesicles. Finally, the anisotropy of DPH fluorescence was found to be invariant with DC15PG content at temperatures just above the liquidus phase line in small, unilamellar vesicles. This demonstrated that inclusion of negatively charged phosphatidylglycerol does not noticeably affect the order within the acyl chain region of the bilayer, relative to phosphatidylcholine.


Favorable factors for re-treatment with pegylated interferon α2a plus ribavirin in patients with high viral loads of genotype 1 hepatitis C virus.
Effect of re-treatment for pegylated interferon (PEG-IFN) plus ribavirin was not fully evaluated. We examined the effects of re-treatment with PEG-IFN plus ribavirin in patients with high viral loads of genotype 1 hepatitis C virus who failed to achieve a sustained virological response (SVR) with combination therapy. We examined 38 patients who were re-treated with PEG-IFN α2a plus ribavirin for more than 60 weeks, among whom 14 were non-responders and 24 were relapsers after previous treatment with PEG-IFN α2b plus ribavirin. IL28B genotyping was done in 21 patients. The overall SVR rate was 34%. Analysis of baseline characteristics showed that the relapsers had a significantly higher SVR rate than the non-responders (50.0%, 12/24 vs. 7.1%, 1/14, respectively, P = 0.012) The SVR rates of re-treated patients who had turned hepatitis C virus (HCV) RNA-negative at weeks 8, 12, 24, and 48 of the previous therapy were 67% (4/6), 67% (4/6), 29% (2/7), and 25% (1/4), respectively. Re-treatment achieved an SVR in five of 12 patients with IL28B major alleles and three of nine patients with IL28B minor alleles. During the re-treatment, patients with complete viral suppression at week-12 achieved a significantly higher SVR rate (P = 0.001). Re-treatment with PEG-IFN α2a plus ribavirin therapy is effective in patients who relapse after a course of PEG-IFN α2b plus ribavirin therapy. Re-treatment is a particularly useful option for patients who achieve early viral clearance during previous therapy.


Corn steep liquor as a cost-effective nutrition adjunct in high-performance Zymomonas ethanol fermentations.
The ethanologenic bacterium Zymomonas mobilis has been demonstrated to possess several fermentation performance characteristics that are superior to yeast. In a recent survey conducted by the National Renewable Energy Laboratory (NREL), Zymomonas was selected as the most promising host for improvement by genetic engineering directed to pentose metabolism for the production of ethanol from lignocellulosic biomass and wastes. Minimization of costs associated with nutritional supplements and seed production is essential for economic large-scale production of fuel ethanol. Corn steep liquor (CSL) is a byproduct of corn wet-milling and has been used as a fermentation nutrient supplement in several different fermentations. This study employed pH-controlled batch fermenters to compare the growth and fermentation performance of Z. mobilis in glucose media with whole and clarified corn steep liquor as sole nutrient source, and to determine minimal amounts of CSL required to sustain high-performance fermentation. It was concluded that CSL can be used as a cost-effective single-source nutrition adjunct for Zymomonas fermentations. Supplementation with inorganic nitrogen significantly reduced the requirement for CSL. Depending on the type of process and mode of operation, there can be a significant contribution of nutrients from the seed culture, and this would also reduce the requirement for CSL. Removal of the insolubles (40% of the total solids) from CSL did not detract significantly from its nutritional effectiveness. On an equal-volume basis, clarified CSL was 1.33 times more "effective" (in terms of cell mass yield and fermentation time) than whole CSL. For fermentations at sugar loading of >5% (w/v), the recommended level of supplementation with clarified CSL is 1.0% (v/v). Based on CSL at US $50/t, the cost associated with using clarified CSL at 1.0% (v/v) is 88 cents/1000 L of medium and 5.3 cents/gal of undenatured ethanol for fermentation of 10% (w/v) glucose. This cost compares favorably to estimates for using inorganic nutrients. The cost impact is reduced to 3.1 cents/gal if there is a byproduct credit for selling the insolubles as animal feed at a price of about US $100/t. Therefore, the disposition of the CSL insolubles can significantly impact the calculations of cost associated with the use of CSL as a nutritional adjunct in large-scale fermentations.


Effects of solvents on the early stage stiffening rate of demineralized dentin matrix.
To monitor the stiffening rate of demineralized dentin matrix at the early stages after exposure to different neat solvents. Dentin beams approximately 0.8x0.7x8.0 mm were obtained from human third molars. After covering their ends with resin composite, the middle exposed length of 4.0mm (gauge-length) was demineralized in 0.5 M EDTA (pH 7.0) for 7 days. The specimens were gripped by a testing machine, pre-loaded to 10 g and cyclically stressed in tension to 5% strain, for 30 repeated cycles (total 20 min) at 0.6 mm/min while immersed in water (control). Then, water was replaced by either 100% acetone, methanol, ethanol, propanol, HEMA or air and the specimens subjected to the same cyclic protocol. The maximum apparent modulus of elasticity (E(Max)) was calculated for every cycle, plotted as a function of time and subjected to regression analysis. Stiffening rate was calculated as changes in E (min). Regression analysis examined the relationship between E and time for each solvent. Data were analyzed by one-way ANOVA and Student-Newman-Keuls test at alpha=0.05. Regression analysis showed that E increased significantly with time in all water-free solvents (R2=0.8-0.99). Stiffening rate was higher for acetone (0.9 MPa/min) and ethanol (0.8 MPa/min), intermediate for air (0.7 MPa/min), methanol (0.6 MPa/min) and propanol (0.5 MPa/min), lower for HEMA (0.2 MPa/min) and practically none for water (0.07 MPa/min) with p<0.05. The solvent-induced stiffening rate of demineralized dentin matrix is both time and solvent-dependent. The ability of solvents to promptly stiffen the demineralized dentin matrix may be important in maintaining the resin-infiltrated matrix expanded during the solvent evaporation stage of resin bonding.


Rat p67 GBP is induced by interferon-gamma and isoprenoid-modified in macrophages.
The guanylate binding proteins, GBPs, are a family of interferon-induced GTP-binding proteins that include the rat p67. We report here that rat p67, for which interferon regulation had not previously been demonstrated, is induced by IFN-gamma and also by LPS in both cultured bone marrow-derived macrophages and microglia. The basal level of rat p67 in macrophages is low but increases dramatically between 2 and 4 hours after treating cells with either IFN-gamma or LPS. It then remains elevated over the next 24 hours. Rat p67 is isoprenoid modified. The isoprenoid modification was detected in p67 isolated both from primary IFN-gamma-activated macrophages and when the gene for p67 was transfected into COS cells. This is the first demonstration of in vivo prenylation of a GBP. The interferon regulation and prenylation of rat p67 point toward this protein being significant in the functions of both activated macrophages and microglia.


Changing Epidemiology of Intestinal Obstruction in Ghana: Signs of Increasing Surgical Capacity and an Aging Population.
This study aimed to describe the epidemiology and outcomes of intestinal obstruction at a tertiary hospital in Ghana over time. Records of all patients admitted to a tertiary hospital from 2007 to 2011 with intestinal obstruction were identified using ICD-9 codes. Sociodemographic and clinical data were compared to a previously published series of intestinal obstructions from 1998 to 2003. Factors contributing to longer than expected hospital stays and death were further examined. Of the 230 records reviewed, 108 patients (47%) had obstructions due to adhesions, 50 (21%) had volvulus, 22 (7%) had an ileus from perforation and 14 (6%) had intussusception. Hernia fell from the 1st to the 8th most common cause of obstruction. Patients with intestinal obstruction were older in 2007-2011 compared to those presenting between 1998 and 2003 (p < 0.001); conditions associated with older age (e.g., volvulus and neoplasia) were more frequently encountered (p < 0.001). Age over 50 years was strong factor of in-hospital death (adjusted OR 14.2, 95% CI 1.41-142.95). Efforts to reduce hernia backlog and expand the surgical workforce may have had an effect on intestinal obstruction epidemiology in Ghana. Increasing aging-related pathology and a higher risk of death in elderly patients suggest that improvement in geriatric surgical care is urgently needed.


[Laboratory evaluation of alpha-cypermethrin insecticide efficacy on Anopheles gambiae populations of Côte d'Ivoire resistant to permethrin and deltamethrin].
Susceptibility tests were carried out in laboratory conditions to evaluate the efficacy of alpha-cypermethrin (a synthetic pyrethroid never used in Côte d'Ivoire) for malaria vector control. Five wild populations of Anopheles gambiae originating from M'bé, Yaokoffikro, Korhogo, Kafiné and Daola and two laboratory reared strains (Kisumu susceptible and Kou permethrin resistant selected strain) were tested. The diagnostic dosage of alpha-cypermethrin for the sensitive strain Kisumu was 2.5 x 10(-3)%. A comparative study of the susceptibility of samples of wild populations of An. gambiae was carried out according to the WHO standard susceptibility test. Impregnated papers with 4% DDT, 0.25% permethrin, 0.025% deltamethrin and 0.0025% alpha-cypermethrin were used. The results showed that except for mosquitoes from M'bé, all the other populations were resistant to these insecticides. Bioassays were carried out with alpha-cypermethrin at the operational dosage of 20 mg a.i./m2 on the same population and laboratory reared strains. The results showed the efficacy of this insecticide on both the Kisumu strain and the population from M'bé, a maintained efficacy for the Daloa, Kafiné and Korhogo mosquito populations, but the wild anopheline population from Yaokoffikro clearly appeared fully resistant.


Selection of recipient vessels in double free-flap reconstruction of composite head and neck defects.
Massive defects of the head and neck regions after resection of advanced carcinoma often require two flaps for optimal reconstruction. This study focuses on the selection of proper recipient vessels. A total of 262 free-flap transfers were performed in 130 patients using the two-flap approach (one patient received two flaps twice). For microvascular anastomosis of inner flaps (intraoral lining-bone reconstruction flaps), the ipsilateral facial artery was used in 56 flaps (42.8 percent), the ipsilateral superior thyroid artery was used in 49 flaps (37.4 percent), and a branch of the internal jugular vein was used as recipient vein in 101 flaps (77.1 percent). For external flaps (soft-tissue-external skin reconstruction flaps), the ipsilateral superior thyroid artery was used in 59 flaps (50.4 percent) and the transverse cervical artery was used in 19 flaps (16.2 percent). In 14 patients the inner flaps provided distal run-off for external flap revascularization. Only seven flaps required vein grafts; they were all used for external face reconstruction (2.8 percent). There were six total (2.3 percent) and 12 partial (4.6 percent) flap failures. Recipient vessel selection and preparation in primary head and neck cancer reconstruction requiring two simultaneous flaps should take into consideration (1) avoidance of unnecessary destruction during tumor ablations and preservation of as many neck vessels as possible, (2) length and diameter match between flap pedicles and recipient vessels to avoid vein grafts, and (3) possible need of another free-flap reconstruction for flap failure, complication, recurrence, or secondary primary cancers. The previously radiated or operated neck does not preclude the use of recipient vessels from that side. Distal run-off of the inner flap for external flap revascularization should be avoided if possible. Once those principles are observed, two-flap reconstruction for primary cancer presents no more difficulties than single-flap reconstruction.


Prostaglandin biosynthesis and stimulation of cyclic AMP in primary monolayer cultures of epithelial cells from mouse mammary gland.
Cyclic AMP levels in primary monolayer cultures of epithelial cells prepared from mid-pregnant mice are stimulated by prostaglandin E1 and E2. Prostaglandin F1alpha and F2alpha have only a slight effect upon cyclic AMP levels. In the absence of phosphodiesterase inhibitors the rise in cyclic AMP produced by PGE1 is only transient and the levels return to normal within 30 minutes. High concentrations (16 mM) of theophylline are needed to prevent this decline, suggesting that the phosphodiesterase activity of epithelial cells in culture is high. However, theophylline alone produced only a small increase in basal cyclic AMP levels even over a 2-hour period indicating that basal cyclic AMP is turned over more slowly than cyclic AMP produced in response to stimulation with PGE1. Both PGE and PGF synthesis were monitored using radioimmunoassay procedures previously reported. The observed levels were found to decrease as cell density increased and were sensitive to the addition of agents such as collagen and naproxen.


Pre-hydrolysis with carbohydrases facilitates the release of protein from brewer's spent grain.
Brewer's spent grain (BSG) is the most abundant side-stream from brewing. It is food-grade being rich in dietary fibre and protein and thus having potential as their source for both food and non-food applications. Initial treatment of milled BSG with a carbohydrase cocktail from Humicola insolens significantly enhanced the subsequent solubilisation of protein from the residual biomass. When treated with an alkaline protease, 76% of BSG protein was solubilized, whereas the yields were significantly lower with neutral or acidic proteases. In alkaline conditions significant amount of protein (53%) as predominantly low molecular weight protein was solubilized even without any protease addition. The degree of protein solubilisation was influenced by the time of exposure of modified BSG to the alkaline environment. The non-enzymatic protein solubilisation was, however, only observed when BSG had been initially treated with the carbohydrase, suggesting the protein is surrounded by cell wall polysaccharides restricting its initial release.


Imaging pain of fibromyalgia.
Brain imaging studies have provided objective evidence of abnormal central regulation of pain in fibromyalgia (FM). Resting brain blood flow studies have reported mixed findings for several brain regions, whereas decreased thalamic blood flow has been noted by several investigators. Studies examining the function of the nociceptive system in FM have reported augmented brain responses to both painful and non-painful stimuli that may be influenced by psychologic dispositions such as depressed mood and catastrophizing. Treatment approaches are beginning to demonstrate the potential for brain imaging to improve our understanding of pain-alleviating mechanisms. Data from other chronic conditions suggest that idiopathic pain may be maintained by similar central abnormalities as in FM, whereas chronic pain conditions with a known nociceptive source may not be. Future neuroimaging research in FM is clearly warranted and should continue to improve our understanding of factors involved in pain maintenance and symptom exacerbation.


The DSM-5 effect: psychological characteristics of new patients affected by Binge Eating Disorder following the criteria of the DSM-5 in a sample of severe obese patients.
The current study evaluated whether or not there were significant differences in psychopathological traits between three groups of individuals. The first was a group of patients seeking bariatric surgery diagnosed as being affected by Binge Eating Disorder (BED), according to the new criteria of the fifth edition of the Diagnostic and Statistical Manual of Mental Disorders. This group (NEW BED group) did not meet BED diagnosis following the previous criteria listed in the DSM-IV-TR. The second group of individuals was composed of severely obese patients seeking bariatric surgery not affected by an eating disorder, according to the diagnostic criteria of the DSM-5 (OB group). The third group was composed of individuals within a healthy weight range (Control group). 94 severely obese patients (33 in the NEW BED group and 61 in the OB group) were compared to the Control group including 41 participants on depression, anxiety and eating habits. The NEW BED scored significantly higher than the OB group on the Beck Depression Inventory, both the subscales of the State Trait Anxiety Inventory, on disinhibition and hunger subscales of the Three-Factor Eating Questionnaire and on many subscales of the Eating Disorders Inventory. The new, less restrictive diagnostic criteria for BED of the DSM-5 are useful in identifying obese patients affected by severe psychopathology and dysfunctional eating habits.