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Diamond Blackfan Anemia (DBA) is a congenital bone marrow failure syndrome associated with ribosomal gene mutations that lead to ribosomal insufficiency. DBA is characterized by anemia, congenital anomalies, and cancer predisposition. Treatment for DBA is associated with significant morbidity. Here, we report the identification of Nemo-like kinase (NLK) as a potential target for DBA therapy. To identify new DBA targets, we screen for small molecules that increase erythroid expansion in mouse models of DBA. This screen identified a compound that inhibits NLK. Chemical and genetic inhibition of NLK increases erythroid expansion in mouse and human progenitors, including bone marrow cells from DBA patients. In DBA models and patient samples, aberrant NLK activation is initiated at the Megakaryocyte/Erythroid Progenitor (MEP) stage of differentiation and is not observed in non-erythroid hematopoietic lineages or healthy erythroblasts. We propose that NLK mediates aberrant erythropoiesis in DBA and is a potential target for therapy. Diamond Blackfan Anemia (DBA) is a congenital bone marrow failure syndrome that is associated with anemia. Here, the authors examine the role of Nemo-like kinase (NLK) in erythroid cells in the pathogenesis of DBA and as a potential target for therapy. [ABSTRACT FROM AUTHOR]

Clinical outcomes after primary graft failure (PGF) remain poor. Here we present a large retrospective analysis (n=23 272) which investigates means to prevent PGF and early detection of patients at high risk. In patients with hematologic malignancies, who underwent their first myeloablative allogeneic hematopoietic cell transplantation, PGF was reported in 1278 (5.5%), and there was a marked difference in PGFs using peripheral blood stem cell compared with bone marrow grafts (2.5 vs 7.3%; P<0.001). A fourfold increase of PGF was observed in myeloproliferative disorders compared with acute leukemia (P<0.001). Other risk factors for PGF included recipient age <30, HLA mismatch, male recipients of female donor grafts, ABO incompatibility, busulfan/cyclophosphamide conditioning and cryopreservation. In bone marrow transplants, total nucleated cell doses ⩽2.4 × 108 per kg were associated with PGF (odds ratio 1.39; P<0.001). The use of tacrolimus-based immunosuppression and granulocyte colony-stimulating factor were associated with decreased PGF risk. These data, allow clinicians to do more informed choices with respect to graft source, donor selection, conditioning and immunosuppressive regimens to reduce the risk of PGF. Moreover, a novel risk score determined on day 21 post transplant may provide the rationale for an early request for additional hematopoietic stem cells. [ABSTRACT FROM AUTHOR]

The impact of extramedullary disease (EMD) in AML on the outcomes of allogeneic hematopoietic cell transplantation (alloHCT) is unknown. Using data from the Center for International Blood and Marrow Transplant Research, we compared the outcomes of patients who had EMD of AML at any time before transplant, with a cohort of AML patients without EMD. We reviewed data from 9797 AML patients including 814 with EMD from 310 reporting centers and 44 different countries, who underwent alloHCT between and 1995 and 2010. The primary outcome was overall survival (OS) after alloHCT. Secondary outcomes included leukemia-free survival (LFS), relapse rate and treatment-related mortality (TRM). In a multivariate analysis, the presence of EMD did not affect either OS (hazard ratio 1.00, 95% confidence interval (CI) 0.91-1.09), LFS (0.98, 0.89-1.09), TRM (relative risk 0.92, 95% CI 0.80-1.16, P=0.23) or relapse (relative risk=1.03, 95% CI, 0.92-1.16; P=0.62). Furthermore, the outcome of patients with EMD was not influenced by the location, timing of EMD, or intensity of conditioning regimen. The presence of EMD in AML does not affect transplant outcomes and should not be viewed as an independent adverse prognostic feature. [ABSTRACT FROM AUTHOR]

Graft failure may contribute to increased morbidity and mortality after allogeneic hematopoietic SCT (allo-HSCT). Here, we present risk factors for graft failure in all first allo-HSCTs performed at our center from 1995 to mid-2010 (n=967). Graft failure was defined as >95% recipient cells any time after engraftment with no signs of relapse, or re-transplantation because of primary or secondary neutropenia (<0.5 × 109/L) and/or thrombocytopenia (<30 × 109/L). Fifty-four patients (5.6%) experienced graft failure. The majority were because of autologous reconstitution (n=43), and only a few patients underwent re-transplantation because of primary (n=6) or secondary (n=5) graft failures. In non-malignant disorders, graft failure had no effect on survival, whereas in malignant disease graft failure was associated with reduced 5-year survival (22 vs 53%, P<0.01). In multivariate analysis, ex vivo T-cell depletion (relative risk (RR) 8.82, P<0.001), HLA-mismatched grafts (RR 7.64, P<0.001), non-malignant disorders (RR 3.32, P<0.01) and reduced-intensity conditioning (RR 2.58, P<0.01) increased the risk for graft failure, whereas graft failures were prevented by total nucleated cell doses of 2.5 × 108/kg (RR 0.36, P<0.01). In conclusion, graft failure was only associated with inferior survival in malignant disease. Non-malignant disorders, HLA match, conditioning intensity, immunosuppression regimen and cell dose all influenced graft failure risk. [ABSTRACT FROM AUTHOR]

Periodic porous structures offer unique material solutions to thermoelectric applications. With recent interest in phonon band gap engineering, these periodic structures can result in reduction of the phonon thermal conductivity due to coherent destruction of phonon modes characteristic in phononic crystals. In this paper, we numerically study phonon transport in periodic porous silicon phononic crystal structures. We develop a model for the thermal conductivity of phononic crystal that accounts for both coherent and incoherent phonon effects, and show that the phonon thermal conductivity is reduced to less than 4% of the bulk value for Si at room temperature. This has substantial impact on thermoelectric applications, where the efficiency of thermoelectric materials is inversely proportional to the thermal conductivity. [ABSTRACT FROM AUTHOR]

Allo-SCT is the only potentially curative regimen for myelodysplastic syndromes (MDSs), but it is associated with a high relapse risk. The role of chimerism analysis for prediction of relapse is yet to be determined. To assess the clinical usefulness of mixed chimerism (MC) for predicting hematological relapse, 75 consecutively transplanted patients with MDS were analyzed with regard to lineage-specific chimerism, encompassing CD33+ cells in peripheral blood (PB, n=49) and CD34+ cells in BM (n= 35). A cutoff of 5% recipient cells was used to discriminate complete donor chimerism from MC. A total of 19 patients (25%) experienced hematological relapse after a median of 5 (1-31) months. Sensitivity for detection of relapse was 59% for CD33+ PB cells and 92% for CD34+ BM cells with corresponding specificities of 91% and 65%. CD34+ BM cells were analyzed before relapse in seven patients, five of whom showed MC at a median of 2.5 (0.5-7) months before relapse. In contrast, 8 of 18 patients showed MC involving CD33 PB with a median of one month (0.5-2) before relapse. Here, we provide a model for early detection of relapse after SCT in MDS, in which serial characterization of both CD33+ PB cells and CD34+ BM cells gives an opportunity for early treatment before overt relapse. [ABSTRACT FROM AUTHOR]

Nanostructured biological materials inspire the creation of materials with tunable mechanical properties. Strong cellulose nanofibrils derived from bacteria or wood can form ductile or tough networks that are suitable as functional materials. Here, we show that freeze-dried bacterial cellulose nanofibril aerogels can be used as templates for making lightweight porous magnetic aerogels, which can be compacted into a stiff magnetic nanopaper. The 20–70-nm-thick cellulose nanofibrils act as templates for the non-agglomerated growth of ferromagnetic cobalt ferrite nanoparticles (diameter, 40–120 nm). Unlike solvent-swollen gels and ferrogels, our magnetic aerogel is dry, lightweight, porous (98%), flexible, and can be actuated by a small household magnet. Moreover, it can absorb water and release it upon compression. Owing to their flexibility, high porosity and surface area, these aerogels are expected to be useful in microfluidics devices and as electronic actuators. [ABSTRACT FROM AUTHOR]

Aims/hypothesis Among diabetic patients, glucose homeostasis may be affected by abnormal gastrointestinal motility and autonomic neuropathy. This study analysed whether oesophageal dysmotility, delayed gastric emptying or autonomic neuropathy affect glucose homeostasis. Materials and methods Oesophageal manometry and gastric emptying scintigraphy were performed in 20 diabetic patients. Heart-rate variation during deep breathing (expiration/inspiration [E/I] ratio) and continuous subcutaneous glucose concentrations for a period of 72 h were also monitored in the same patients. Results Oesophageal dysmotility was found in eight of 14 patients. Eleven of 20 patients had delayed gastric emptying (abnormal gastric emptying half-time [T50]) and nine of 18 had an abnormal E/I ratio. Complaints of abdominal fullness were predictive of delayed gastric emptying. A low peristaltic speed of the oesophagus was associated with impaired T50 (rs=-0.67; p=0.02). One hour after breakfast, subcutaneous glucose levels decreased in patients with delayed gastric emptying but continued to rise in those with normal emptying. Consequently, the median glucose level 2.5 h after breakfast was lower in the former (9.1 [4.2–12.5] vs 14.3 [11.2–17.7] mmol/l; p<0.05). Glucose fluctuations during the 72 h were significantly higher in patients with an abnormal E/I ratio than in those with a normal E/I ratio (coefficient of variation: 41 [46–49] vs 28 [27–34]%; p=0.008). Conclusions/interpretation Abdominal fullness predicted delayed gastric emptying that was associated with diminished glucose uptake after breakfast. Low oesophageal peristaltic speed was associated with slow gastric emptying whereas parasympathetic neuropathy was associated with increased glucose variations. [ABSTRACT FROM AUTHOR]

Aims/hypothesis: We recently found evidence of an angiotensin-generating system in pancreatic islets. The present study investigated the effect of endogenously produced angiotensin II on microcirculation and function in transplanted islets. Materials and methods: Losartan, an angiotensin II type 1 receptor inhibitor, was administered either acute intravenously to mice with 4-week-old islet renal subcapsular transplants, or added to the drinking water for the final 14 days or throughout the 4-week post-transplantation period. The graft-bearing kidney was, in some cases, dissected out and perfused in vitro to evaluate the effect of angiotensin II and losartan on glucose-stimulated insulin release from the grafts. Results: Losartan treatment throughout the 4-week post-transplantation period had negative effects on islet revascularisation as well as on islet graft insulin release. However, administration of losartan, either intravenously or orally, after the formation of a new vascular network, improved islet graft blood perfusion. PO2 in the islet transplants was also effectively improved by the losartan treatment. Graft perfusion experiments showed a markedly better first phase of glucose-stimulated insulin release in transplanted islets when exposed to losartan. In contrast, acute administration of angiotensin II decreased islet graft blood flow, PO2 and glucose-stimulated insulin release. Conclusions/interpretation: This study shows that inhibition of the islet reninangiotensin system may be a feasible strategy to increase the blood perfusion, PO2 and function within islet grafts. Such treatment should not be initiated, however, before the islet vascular system has been formed. [ABSTRACT FROM AUTHOR]

Aims/hypothesis: Recent studies suggest that donor endothelial cells may contribute to islet graft re-vascularisation. Since islet endothelial cells disappear during culture, we hypothesised that transplantation of islets without prior culture is beneficial for their engraftment. Methods: Cultured (4-7 days) or freshly isolated islets (<4 h after donor pancreas extirpation) were syngeneic- ally transplanted into Wistar-Furth rats and C57B1/6 mice beneath the renal capsule. Islet graft revascularisation was evaluated by measuring vascular density, blood flow and tissue oxygen tension. Islet graft function was investigated by a minimal islet mass model in inbred mice (C57B1/6). Results: Four days after implantation, the partial pressure of oxygen (pO2) in the transplanted cultured islets was less than 10 mmHg (1.33 kPa), but tended to be higher in grafts composed of freshly isolated islets. The pO2 in the grafts of freshly isolated islets had more than doubled 4 weeks later, whereas the PO2 in the grafts of cultured islets remained at values similar to those recorded 4 days after transplantation. Transplanted freshly isolated islets also had a higher vascular density than transplanted cultured islets (∼40 vs ∼25% of that in endogenous islets) when investigated I month post-implantation. When applying a minimal islet mass model in inbred mice, 200 freshly isolated islets cured alloxan-diabetic mice in all cases, whereas only 33% of the group receiving similar numbers of cultured islets were cured. Conclusions/interpretation: Transplantation of pancreatic islets without prior culture is beneficial for their vascular engraftment and function. [ABSTRACT FROM AUTHOR]

Rationale: Clozapine is a unique antipsychotic, with efficacy against positive symptoms in treatment-resistant schizophrenic patients, and the ability to improve cognition and treat the negative symptoms characteristic of this disease. Despite its unique clinical actions, no specific molecular mechanism responsible for these actions has yet been described. Objectives and methods: To comprehensively profile a large library of neuropsychiatric drugs, including most antipsychotics, at human monoamine receptors using R-SAT, an in vitro functional assay. Results: Profiling revealed that N-desmethylclozapine (NDMC), the principal metabolite of clozapine, but not clozapine itself, is a potent and efficacious muscarinic receptor agonist, a molecular property not shared by any other antipsychotic. To further explore the role of NDMC muscarinic receptor agonist properties in mediating the physiological actions of clozapine, systemically administered NDMC was found to stimulate the phosphorylation of mitogen-activated protein kinase (MAP kinase) in mouse CA1 hippocampal neurons, an effect that was blocked by scopolamine, confirming central M1 muscarinic receptor agonist activity in vivo. Lastly, an analysis of clozapine and NDMC serum levels in schizophrenic patients indicated that high NDMC/clozapine ratios better predicted improvement in cognitive functioning and quality of life than the levels of either compound alone. Conclusions: The muscarinic receptor agonist activities of NDMC are unique among antipsychotics, and provide a possible molecular basis for the superior clinical effects of clozapine pharmacotherapy. [ABSTRACT FROM AUTHOR]

Thin films of 3,4-epoxycyclohexylmethyl 3'4'-epoxycyclohexane carboxylate were UV irradiated (1.1 J cm-2) under isothermal conditions ranging from 0 to 50°C. Under these conditions the polymerization advanced quickly but only to a conversion level of less than 10% before the reaction rate slowed by more than an order of magnitude. This drop off in rate was not caused by the glass transition temperature, Tg, reaching or exceeding the reaction temperature, Trxn, since the epoxide's Tg remained at least 40°C below Trxn. Raising the sample temperature above 60°C caused a sharp increase in the conversion level. At 100°C conversion exceeds 80% and the ultimate Tg approaches 190°C. The addition of 10 mass% I ,6-hexanediol, HD, to the epoxy caused the conversion at room temperature to quintuple over the level obtained without the alcohol present. The heat liberated from this alcohol epoxy blend during cure on a UV conveyor belt system caused the sample's temperature to increase by about 100°C above ambient whereas the epoxy alone under these conditions only experienced a modest temperature rise of about 26°C. If the amount of HD in the blend is increased above 10% the heat of reaction at 23°C decreases due to ND being trapped in a nonreactive crystalline phase. Boosting reaction temperatures above 50°C melts the HD crystals and yields significantly improved conversion ratios. As the level of alcohol blended with the epoxy is raised its ultimate Tg is lowered and when the concentration of alcohol in the blend nears 30 mass% Tg drops below room temperature. [ABSTRACT FROM AUTHOR]

The disordered vortex phases induced by line and point pinning in YBa2Cu3O7−δ are explored. At high defect densities, only a single disordered solid separated from the liquid phase by a melting line is observed. At low defect densities the topology of the phase diagram changes dramatically, with a vortex lattice phase adjoining disordered phases at high or low field. Critical points at the termination of the first-order melting line separate the lattice and the disordered phases. The line defect disordered phases follow the expected Bose glass behavior, while the point defect disordered phases do not exhibit the expected vortex glass behavior. [ABSTRACT FROM AUTHOR]

Nine patients (6 males, 3 females) with biopsy-proven liver cirrhosis participated in an open, cross-over, three centre study of the effect of impaired liver function on the pharmacokinetics of felodipine. Two of the nine patients had undergone porto-caval anastomosis. Each patient was given 0.75 mg i.v. and 10 mg p.o. on separate occasions. The results of this study have been compared with published data from younger subjects and elderly hypertensive patients. The mean peak plasma concentration normalized to a dose of 10 mg (C 46 nmol/l) was twice as high in the cirrhotic patients as in the healthy subjects, but the bioavailability, f, (17.0%) was comparable. Subjects with a porto-caval shunt did not have higher f than the mean for the group. The volume of distribution at steady-state, V, was significantly lower than in the healthy subjects. Protein binding was significantly lower in the patients with cirrhosis: 99.46% compared to 99.64% in the healthy subjects. The weight-corrected clearance was 1/3 of the value in healthy subjects. No correlation between systemic availability and oral clearance was found, so it is proposed that felodipine is metabolized both in the liver and also in the gut wall. The results suggest that at least the starting dose should be reduced in patients with severe liver disease. [ABSTRACT FROM AUTHOR]

A study has been made of the reaction equilibria in the manganese sulfate, sulfide, and oxide systems. By equilibrating manganese oxides (MnO, MnO) with SO + O + N gas mixtures, the dissociation pressures of MnSO have been evaluated. It was also found that there is some sulfate solid solution in manganese oxides. The equilibrium gas composition for the formation of manganese sulfide from manganous oxide was determined by reacting the oxide with H2-H2S-HO mixtures. The manganese sulfide was found to be more stable than indicated by previous studies. It was also found that there is little or no solid solution of sulfide in manganous oxide. This is contrary to the previously reported observations. The chemistry of reactions involved in the production of mattes in a low-shaft blast furnace is discussed in the light of our recent studies of sulfate-sulfide reactions. [ABSTRACT FROM AUTHOR]

Opsin-immunoreactive sites in the eye and optic nerve of the hagfish, Myxine glutinosa, were studied by use of light-microscopic pre- and postembedding peroxidase-antiperoxidase or avidin-biotin-peroxidase techniques, and the immuno-electron-microscopic protein A-gold method. At the light-microscopic level, a strong opsin immuno-reaction was obtained on the outer segments of the photoreceptor cells with sheep and rat antibodies against bovine (rhod)opsin. These outer segments were located in the marginal photoreceptor space and in follicles of the retina, as well as in the tubular lumen of the optic nerve. Ultrastructurally, two classes of outer segments can be distinguished; most of them exhibited a strong antiopsin reaction, while certain elements lacked immunoreactivity with the antisera employed. The protein A-gold particles marked opsin-immunoreactive sites on the photoreceptor membranes. The presence of opsin-immunoreactive material in the retina and optic nerve of the hagfish strengthens the view that this primitive eye lacking a cornea, lens and vitreous body is engaged in light perception. The morphological similarity between the eye and pineal tissue is discussed in connection with the absence of a pineal organ in this species. [ABSTRACT FROM AUTHOR]

The pineal complex of Lampetra fluviatilis, Anguilla anguilla and Salmo gairdneri was studied by means of the indirect immunohistochemical antiopsin reaction. Opsin-immunoreactive material was demonstrated in the outer segments of the photoreceptor cells in the pineal organ of all three species investigated. In the lamprey, the opsin-positive outer segments were located in the lumen of the pineal vesicle and atrium. In the two teleost species, the immunoreactive outer segments were observed in abundance in the pineal end-vesicle and stalk. These structures were found to accumulate in the prominent initial portion of the pineal stalk of the eel. In the rainbow trout, immunoreactive outer segments occurred in the wide orifice of the pineal recess at the roof of the third ventricle. In addition, outer segments of photoreceptor cells of the parapineal organ ('parapinealocytes') displayed opsin immunoreactivity. In the lamprey, opsin immunoreactivity was restricted to the central portion of the ventral parapineal retina, while the parapinealocytes in the lateral portions did not bind the antibody. In the two teleosts, immunoreactive outer segments displayed a scattered pattern. These immunocytochemical results provide direct evidence that the photosensitivity of the pineal demonstrated electrophysiologically in lampreys and teleosts (cf. Dodt 1973) is based on an opsin-containing photopigment. The presence of opsin in cells of the parapineal organ strengthens the view that also this organ may be capable of direct light perception. In the lamprey, the exclusive opsin immunoreactivity of a circumscribed group of parapineal cells suggests the existence of two types of parapinealocytes. The significance of opsin-containing photoreceptor outer segments occurring in the most proximal portion of the teleost pineal stalk is discussed, especially with regard to the interpretation of results obtained from pinealectomy experiments. [ABSTRACT FROM AUTHOR]

Pharyngeal constrictor paresis (PHCP) is sometimes found in videoradiography of the swallowing act in patients complaining of dysphagia. Ten patients with PHCP and 10 dysphagic, age- and sex-matched controls with normal videoradiography were neurologically evaluated and examined with magnetic resonance imaging (MRI) of the brain and brainstem in order to learn the pathogenetic process behind PHCP. The study revealed 8 PHCP patients and 1 dysphagic control with abnormal clinical neurological findings such as myopathy, cerebrovascular disease, or extrapyramidal disease. The neurological examination revealed considerable information of prognostic and therapeutic value in PHCP patients. The MRI was abnormal in 7 PHCP patients and 4 dysphagic controls. However, the findings in MRI were nonspecific but the examination was found to be valuable in selected cases. It is concluded that PHCP is an indicator of neurological disease and accordingly, such patients should be examined by a neurologist to establish the cause of the disease. [ABSTRACT FROM AUTHOR]

To study the influence of bolus size on pharyngeal swallow, 20 dysphagic patients and 10 nondysphagic volunteers were examined cineradiographically while swallowing a bolus of 2.5, 5, 10, and 20 ml. Ten patients and 10 volunteers swallowed boluses in increasing volume while 10 patients swallowed boluses of decreasing volume. The movement of the hyoid bone occurred in a two-step fashion irrespective of the bolus size, and in all individuals. The speed of the apex of the bolus through the pharynx, measured by frame counting, increased with increasing size of the bolus. The speed of the peristaltic wave, as measured between vallecula and the PE segment, did not change with bolus size. Boluses of 10 or 20 ml caused penetration of barium into the larynx in 7 of the patients but in none of the volunteers. Our results suggest that pharyngeal constrictor activity, in terms of speed of peristalsis, is constant and not influenced by bolus volume. [ABSTRACT FROM AUTHOR]

The larval endostyle consists of two ridges of secretory cells, which correspond to the two paired muciparous bands in the endostyles of the adult Branchiostoma, most tunicates, and the lamprey ammocoete. The peculiar shape of the larval endostyle is an effective adaption for food-trapping in the asymmetrical body of the larva. Contrary to general belief, the internal opening of the club-shaped gland is the site of the secretory release, while the exernal opening is an inlet for sea water. The water is mixed with the mucous substance, probably containing neutral glycoproteins, which is produced in the gland tube. This material is released through the internal pore dorsally in the buccal cavity at a position where it is carried with the endostylar secretion towards the intestine. The club-shaped gland is not part of the food-trapping mechanism, but it is apparently an important larval gland which produces substances which may act in the processing of the food or in some other way may direct larval life. [ABSTRACT FROM AUTHOR]

The ability of a series of N-modified N-alkyl-5′-uronamides to cause presynaptic inhibition of transmitter release was examined in isolated guinea-pig ileum stimulated at 0.2 Hz. These analogs inhibited the twitch responses to nerve stimulation, the majority being full agonists with their inhibitory effects being antagonised by theophylline. These analogs had no significant effects on responses of ileum to carbachol. N-ethyl 5′-uronamide substitution resulted in an up to four-fold reduction in activity of N-substituted adenosine analogs, while stereoselectivity of the N-substituted analogs continued to be present. 5′-Uronamide substitutions to N-(3-pentyl)-adenosine resulted in a marked loss of activity when there were large alkyl groups at the amide or with amides of secondary amines. It was concluded that adenosine analogs interact with both the N6 and C-5′ regions of the adenosine receptor in this tissue, with the interaction being less than additive. [ABSTRACT FROM AUTHOR]

This study explored the nature of the purine domain N regions of the presynaptic adenosine receptors of guinea-pig ileum and of rat vas deferens. The experimental design tested a model of these receptors which is complementary to the structure of the N substituent of the classical A adenosine receptor agonist N-1-phenyl-2R-propyladenosine, ( R-PIA). Assays of activity employed ileal segments or the midportions of vasa deferentia under continuous electrical stimulation at 0.2 Hz. Structure activity correlations compared the EC-50s for twitch inhibition. As shown previously, R-PIA was 60-80 times more potent than its S diastereomer, the resultant of the positive contribution of propyl C-3 to activity as well as the negative influence of steric hindrance exerted by propyl C-3 of the S diastereomer. Other pairs of diastereomers having a chiral center adjacent to N showed that the stereoselectivity of the PIAs was generalizable. Biological activity appears to reside wholly in the N alkyl moiety; the phenyl or aryl groups of similar size actually diminished potency. The receptor subregions interacting with propyl C-1 and C-3 of R-PIA are each large enough to accomodate two - but not three - methylene residues, each methylene contributing additively to activity. Hydrophobicity is a prominent attribute of the propyl C-1 and C-3 subregions. The potencies of these analogs as inhibitors of presynaptic transmission in ileum or vas deferens are covariant with inhibition of [H]N-cyclohexyl-adenosine binding to rat cerebral cortical membranes. Singular exceptions to this generalization may represent organ- or species-dependent differences in receptor fine structure. [ABSTRACT FROM AUTHOR]

This study compares the coronary vasoactivity of acetate in the blood-perfused heart of the open-chest dog and in the buffer-perfused guinea-pig heart. In the dog acetate is a weak but probably fully efficacious coronary agonist. Direct intracoronary infusions of isosmolar Na acetate caused dose-dependent coronary vasodilation and decreased transcoronary O extraction, resulting in an increase in cardiac O usage of up to 40%. Acetate raised coronary flow to at least 50% above control in 63 of 67 dogs but caused maximum coronary vasodilation (400% of control) in only 39 of the 67. The frequency distribution of the acetate EC-20 decreased monotonically from a mode at <1 mM over a range extending to >6 mM, suggesting a single population of animals characterized by a rather wide range of sensitivity to acetate. Theophylline antagonized acetate vasodilation, in support of the idea that adenosine mediates the coronary effects of acetate. In the guinea-pig heart, acetate in concentrations up to 10 mM caused minimal increases in coronary flow that were completely accounted for by the small change in O usage that resulted from switching from glucose to acetate the main energy source. Acetate (10 mM) elicited a small release of adenosine and its degradation products. [ABSTRACT FROM AUTHOR]

Objective: Dynamic barium radiology with cine- or video recording has been the most frequently used technique for assessing patients with pharyngeal dysphagia. Although the diagnostic yield of the barium swallow has been high, many patients with pharyngeal dysphagia have normal dynamic barium radiology and remain a diagnostic dilemma. Could manometry add important diagnostic information in these patients?Material and Methods: We examined 19 patients (12 men and 7 women, mean age 47 years, range 19-69 years) with pharyngeal dysphagia but a normal barium swallow with simultaneous videoradiography and pharyngeal manometry and compared their manometry to that found in 24 normal volunteers (11 men and 13 women, mean age 37 years, range 23-59 years).Results: Comparing mean values, the patient group showed statistically significant differences from the control group for eight of 10 manometric parameters. Fourteen of 19 patients showed at least one (five patients) and in most cases multiple (nine patients) manometric abnormalities (values exceeding normal mean by +/- 2SD) which might have contributed to their dysphagia: five patients with high upper esophageal sphincter (UES) resting pressures, five with high UES residual pressures, three with weak pharyngeal contractions, three with pharyngeal "spasms," seven with prolonged contraction/relaxation times, five with reduced compliance, and seven with UES/P incoordination.Conclusions: Solid-state computerized manometry is a useful adjunct to videoradiography and can provide potentially important additional information in the diagnosis of dysphagia patients. [ABSTRACT FROM AUTHOR]

In this work the effect of additions of H, HO, CO, SO, and HS on the catalytic decomposition of CO by iron has been investigated at 400, 600, and 800°C and atmospheric pressure. The catalyst was porous iron formed by the reduction of hematite ore granules with hydrogen. The relative importance of carbon deposition by the reactions 2CO → C + CO and H + CO → C + HO was determined as a function of hydrogen concentration. It was found that even low concentrations of hydrogen greatly enhanced the rate of decomposition of CO, presumably by a catalytic action of adsorbed hydrogen on iron. The presence of water vapor had a dual effect. At low concentrations of hydrogen the rate of decomposition of CO increased with the addition of HO, apparently by a catalytic effect. At high concentrations of hydrogen, however, carbon deposition was retarded because of the effect of the reverse reaction HO + C → H + CO. In CO-CO mixtures the rate of carbon deposition decreased with increasing CO content, because of the effect of the reverse reaction CO + C → 2CO. The presence of traces of sulfur-bearing gaseous species, such as SO and HS, retarded the decomposition of CO on iron and brought about the early cessation of carbon deposition. This strong effect may be due to the retardation of the decomposition of the intermediate product, cementite, and the formation of pyrrhotite on the surface of the iron catalyst. [ABSTRACT FROM AUTHOR]

The pore structure of iron reduced from hematite ore by hydrogen is charactertized from measurements of pore volume, pore area and effective gas diffusivity. The measured connected pore volume within the range 0.22 to 0.34 cu cm per g is about the same as the total pore volume; that is, most of the pores in the reduced iron are interconnected. The pore area measured by the BET technique increases with decreasing reduction temperature, e.g. from 0.1 sq m per g at 1200°C to 39 sq m per g at 200°C. The effective H−HO diffusivity, measured directly at 600°C after reduction of the ore in hydrogen at the same temperature, is in excellent agreement with that derived from the reduction data. The pore-diffusivity measurements were also made at room temperature using iron samples reduced in hydrogen at 800° and 1000°C. On the basis of the pore properties measured, it appears that the reduced iron has a regular pore structure which becomes finer with decreasing reduction temperature. The effective diffusivities computed on the basis of a simple pore structure are found to be in accord with those derived previously from the reduction data. [ABSTRACT FROM AUTHOR]

Measurements were made of the rate of equimolar counterdiffusion of hydrogen and water vapor through porous iron formed by the reduction of dense hematite, magnetite, and commercial iron ore pellets with hydrogen. The experiments were conducted at temperatures between 400° and 1000°C and at pressures between 0.1 and 40 atm. It is demonstrated that the structure of the porous iron is primarily a function of reduction temperature and that the diffusion process at the higher reduction temperatures is normal. The effect of gaseous diffusion on the rate of reduction of dense hematite with hydrogen is discussed. It is shown that gaseous diffusion limits the rate at the higher temperatures and pressures. [ABSTRACT FROM AUTHOR]

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Copyright of Ingenieur-Archiv is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Ingenieur-Archiv is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Ingenieur-Archiv is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Ingenieur-Archiv is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Ingenieur-Archiv is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Ingenieur-Archiv is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Ingenieur-Archiv is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Ingenieur-Archiv is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

An extensive basal cell carcinoma of the mid-parietal scalp penetrating the skull and invading the posterior third of the superior sagittal sinus was successfully treated in a 60-year-old man. This was accomplished by gradually obstructing the sinus over a period of five weeks unit it was possible to resect the tumor along with 15 cm of the sagittal sinus. Total obstruction of the sinus was achieved using two miniature tissue expanders surgically placed and affixed to the vessel. By gradual filling of the expanders, it was possible, after five weeks, to demonstrate angiographically that the sagittal sinus between the two tissue expanders was obliterated. The one piece resection included a wide margin of skin, bone, dura mater and sagittal sinus. The extensive defect of the dura mater was covered by a free fascia lata graft and the scalp defect by a visor bipedicled forehead flap. The forehead donor area was skin grafted. There were no complications during surgery and the patient recovered uneventfully. There has been no recurrence after one year. [ABSTRACT FROM AUTHOR]

The article presents a case report of a 64-year old woman who had renal cell carcinoma and then suffered ethmoiditis. During admission, she was subjected to allogeneic haematopoietic stem cell transplantation (HSCT) to foster graft versus tumor effect. Tacrolimus and sirolimus were some of the medications being administered during recovery. However, the patient posed complaints on frontal headache at the area of the right eye and nausea which later further impaired vision of the right eye.

Copyright of European Journal of Wood & Wood Products / Holz als Roh- und Werkstoff is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)