Factors affecting the surgical outcomes of tethered cord syndrome in adults: a retrospective study.
This study aimed to find the factors that may affect the surgical outcomes of congenital tethered cord syndrome (TCS) in adults by evaluating the long-term surgical outcomes of 25 consecutive cases. Medical records of 79 TCS cases which underwent surgery in Bakırköy Research and Training Hospital for Neurology, Neurosurgery and Psychiatry (BRSHH), during an 11-year period from 2005 to 2015, were retrospectively reviewed. All adult cases (patient age > 18 years) were selected as the core sample used for this study. Twenty-five cases of TCSs were surgically treated. The sample consists of 16 female and nine male patients. The mean age of the sample is 30.1 ± 10.3 years. Untethering was carried out in 88% of the patients. Sixty-four percent of the patients had good clinical outcomes at their last follow-up (after 73.8 months on average). The mean length of hospital stay was 4.76 ± 2.88 days. In a multivariate regression model, laminectomy, bladder dysfunction when associated to muscular weakness, and long-term (>6 months) symptoms were selected as the independent risk factors associated with poor or minimally improved (almost unchanged) surgical outcomes. When the urodynamic test showed overactive detrusor muscle, no improvement was recorded in postoperative urodynamic test. Laminoplasty (or hemilaminectomy), short-term (<6 months) symptoms, patients without lipomas, and presentation with moderate or mild symptoms seem to be proper predictors for good surgical outcomes. Further prospective studies are necessary to investigate these findings systematically. Urodynamic study can be used as a predictive tool for close follow-up of asymptomatic adult patients involved with TCS.


Vitamin D Toxicity; Stored and Released from Adipose Tissue?
Vitamin D is a pro-hormone that plays an important role in body calcium regulation. Vitamin D toxicity occurs rarely due to its wide therapeutic index. A 38-year-old Iranian man was admitted to our hospital with a diagnosis of vitamin D toxicity. Laboratory test revealed hypercalcemia and elevated 25-hydroxyvitamin D (25(OH)D) level. Despite the cessation of vitamin D intake and diuretic treatment, he presented four months later with high 25(OH)D level and similar clinical features. Due to the potential release of vitamin D from adipose tissue, serial monitoring of 25(OH)D level is recommended.


[The role of the complement system in the pathogenesis of yersinioses].
In 95 patients with Yersinia infections (yersiniosis and pseudotuberculosis) the character of changes in the complement system was studied, taking into account the functional activity of C1-C5, Co. The study demonstrated a decrease in the activity of the complement system in the dynamics of Yersinia infections and revealed quantitative changes of characteristics in yersiniosis and pseudotuberculosis. The results of the study suggest the mobilization of the complement system in Yersinia infections by the classical path of activation. Regularities of changes in the activity of C1-C5, Co, corresponding to the severity and clinical variants of Yersinia infections, make it possible to recommend the use of the above-mentioned parameters in the clinic of infectious diseases for evaluating the effectiveness of treatment and the course of the disease.


Speech rate adjustment of adults during conversation.
Speech rate convergence has been reported previously as a phenomenon in which one's speech rate is influenced by his/her partner's speech rate. This phenomenon has been demonstrated in artificial settings, and to some extent, in mother-child interactions. The purpose of this study was to explore speech rate adjustment in a quasi-natural adult-adult conversation. An A-B-A-B paradigm was used, in which ten adults conversed on a given topic with two experimenters. Speech rates of both communication partners were measured. Participants significantly reduced their speech rate, in response to the experimenters' reduction in speech rate. However, the participants' reduction in speech rate was significantly smaller than the experimenters' reduction in speech rate. In addition, during the controlled slow speech rate, the participants' speech rate correlated negatively with that of the experimenters'. Results suggest that speech rate convergence is a non-linear phenomenon, and may be affected by various linguistic as well as communicational factors. From a clinical perspective, the results support the use of the modeling strategy in speech therapy, as a means to facilitate a reduction in clients' speech rate.


High resolution NMR solution structure of the leucine zipper domain of the c-Jun homodimer.
The solution structure of the c-Jun leucine zipper domain has been determined to high resolution using a new calculation protocol designed to handle highly ambiguous sets of interproton distance restraints. The domain comprises a coiled coil of parallel alpha-helices in which most of the hydrophobic residues are buried at the highly symmetrical dimer interface; this interface extends over 10 helical turns and is the most elongated protein domain solved to date using NMR methods. The backbone fold is very similar to that seen in crystal structures of the GCN4 and Jun-Fos leucine zippers; however, in contrast with these crystal structures, the Jun leucine zipper dimer appears to be devoid of favorable intermolecular electrostatic interactions. A polar asparagine residue, located at the dimer interface, forms the sole point of asymmetry in the structure; furthermore, the side chain of this residue is disordered due to motional averaging. This residue, which is highly conserved in the leucine zipper family of transcription factors, provides a destabilizing influence that is likely to facilitate the rapid exchange of zipper strands in vivo.


Aorticopulmonary fistula. A case of successful repair with review of literature since 1943.
A case of aorticopulmonary fistula secondary to thoracic aortic aneurysm of syphilitic origin has been presented. Aneurysm involved the first portion of the ascending aorta and ruptured into the main pulmonary artery a few cm above the pulmonic valve. Two weeks after onset, the patient successfully operated upon under profound hypothermia with perfusion. Thirteen cases of this disease since 1943 were reviewed and we discussed briefly profound hypothermia as a useful technic for surgical correction of this condition.


Towards a lattice-matching solid-state battery: synthesis of a new class of lithium-ion conductors with the spinel structure.
Lithium ion batteries have conquered most of the portable electronics market and are now on the verge of deployment in large scale applications. To be competitive in the automotive and stationary sectors, however, they must be improved in the fields of safety and energy density (W h L(-1)). Solid-state batteries with a ceramic electrolyte offer the necessary advantages to significantly improve the current state-of-the-art technology. The major limit towards realizing a practical solid-state lithium-ion battery lies in the lack of viable ceramic ionic conductors. Only a few candidate materials are available, each carrying a difficult balance between advantages and drawbacks. Here we introduce a new class of possible solid-state lithium-ion conductors with the spinel structure. Such compounds could be coupled with spinel-type electrode materials to obtain a "lattice matching" solid device where low interfacial resistance could be achieved. Powders were prepared by wet chemistry, their structure was studied by means of diffraction techniques and magic angle spinning NMR, and Li(+) self-diffusion was estimated by static NMR line shape measurements. Profound differences in the Li(+) diffusion properties were observed depending on the composition, lithium content and cationic distribution. Local Li(+) hopping in the spinel materials is accompanied by a low activation energy of circa 0.35 eV being comparable with that of, e.g., LLZO-type garnets, which represent the current benchmark in this field. We propose these novel materials as a building block for a lattice-matching all-spinel solid-state battery with low interfacial resistance.


Renal, endocrine and vascular effects of atrial natriuretic peptide in a novel vasopressin-deficient genetically hypertensive strain of rat.
In the absence of the potentially confounding influence of vasopressin in hypertension, the effects of atrial natriuretic peptide (ANP) on arterial blood pressure and renal handling of water and sodium were assessed from comparison of responses to intravenous ANP infusion in anaesthetized vasopressin-deficient New Zealand genetically hypertensive (DI/H) rats and their normotensive substrain (DI/N). After 320 min of hypotonic saline infusion, plasma ANP concentration was significantly higher in DI/H compared with DI/N rats. ANP administration increased circulating ANP concentration in both groups. Plasma angiotensin II concentration was higher in DI/H than in DI/N rats; infusion of ANP raised circulating angiotensin II in both groups though this achieved statistical significance only in DI/N rats. Plasma aldosterone concentrations were initially similar in normotensive and hypertensive animals and, in both, were reduced markedly by I.V. ANP infusion. Administration of ANP produced sustained hypotension in both groups. However, the hypotensive effect of ANP was more pronounced in DI/H compared with DI/N rats. Heart rate was initially similar in the two groups, and infusion of ANP produced no detectable change. By comparison with animals maintained on hormone-free infusate, urine flow increased markedly over the 80 min period of ANP infusion in both groups, by 142% in DI/H rats and 127% in DI/N rats. ANP administration produced a natriuresis in both groups but the increase in Na+ excretion was much greater in DI/H (342%) than in DI/N (139%) rats. It appears from the current study that vasopressin-deficient hypertensive rats are more sensitive to ANP with regard to effects on blood pressure and renal excretion than their vasopressin-deficient normotensive substrain. These differences may, in part, reflect adjustments to long-term elevation in blood pressure and in plasma ANP concentration in hypertension and, in part, rely on the associated disturbances in related endocrine systems.


Monitoring radiant power in the critically ill newborn under a radiant warmer.
To evaluate radiant power received by infants under radiant warmers, 11 neonates (mean gestational age 32.2 weeks, mean weight 1.50 kg) were monitored. A wattmeter was used to evaluate warmer power (watts), and a thermopile placed at bed level was used to correlate warmer power to radiant power density received (mw/cm2). Warmer power ranged from 133-301 watts. A linear relationship existed between warmer power and radiant power density received (r = 0.97, p < 0.001). After establishing that radiant power delivery could be monitored with a wattmeter, this technique was used to quantitate radiant power in a small series of infants with and without a plastic shield. Radiant power density received decreased in all infants when shielded (mean 14.6-11.2 mw/cm2, p < 0.01). This study demonstrates: (1) radiant warmer power can be monitored with a wattmeter; (2) warmer power correlates to radiant power density received; and (3) radiant power monitoring can be used to evaluate radiant power demands in specific clinical situations.


17β-Estradiol/extrogen receptor β alleviates apoptosis and enhances matrix biosynthesis of nucleus pulposus cells through regulating oxidative damage under a high glucose condition.
Hyperglycemia in the Diabetes mellitus (DM) patients is a potential etiology of disc degeneration. 17β-estradiol (17β-E2) supplementation plays an anti-diabetic role in DM patients. This study was aimed to investigate the role and mechanism of 17β-E2 in regulating nucleus pulposus (NP) cell apoptosis and NP matrix production under a high glucose condition. Rat NP cells were cultured in medium with a high glucose concentration (0.2 M). 17β-E2 was added into the culture medium to investigate its protective effects. The ERβ inhibitor PHTPP and ERβ activator ERB041 were used to investigate the effects of ERβ. NP cell apoptosis was analyzed by flow cytometry and expression of apoptosis-related molecules. NP matrix production was evaluated by expression of matrix macromolecules. Additionally, intracellular reactive oxygen species (ROS) content was also detected. Compared with the control NP cells, 17β-E2 decreased NP cell apoptosis ratio, down-regulated gene expression of Bax and caspase-3, up-regulated gene expression of Bcl-2, increased protein expression of cleaved PARP and cleaved caspase-3, and increased expression of matrix molecules (aggrecan and collagen II). Moreover, 17β-E2 decreased ROS content. Further analysis showed that ERβ inhibition partly reversed these effects of 17β-E2 whereas ERβ activation further promoted its effects. 17β-E2/ERβ interaction attenuates apoptosis and promotes matrix biosynthesis of NP cells through alleviating oxidative damage under a high glucose condition. This study provides new knowledge on strategies for retarding disc degeneration.


[From the history of thrombosis prevention and treatment].
Rudolf Virchow described not only his famous triad in the 1840s but also the relationship between thrombosis and pulmonary embolism. Deep vein thrombosis (DVT) was recognized as postoperative complication from the 1890s. The preventive measures were directed against the factor blood stasis until heparin was applied clinically in the 1930s. The Swiss surgeon K. Lenggenhager was probably the first who recommended low dose heparin prophylaxis in 1940 on a rational experimental basis. Perhaps because his results were published only in German this application form became not popular before the great studies of Kakkar in the 70s took place. The introduction of low molecular weight heparins in the 80s simplifies prophylaxis and therapy of DVT again. The descriptions of deficiency of natural coagulation inhibitors start with antithrombin III in 1961. The recent discovery of the molecular basis of activated protein C resistance made history today.


Binding of tsHMG, a mouse testis-specific HMG-domain protein, to cisplatin-DNA adducts.
The anticancer drug cisplatin is particularly effective against testicular tumors. Although the clinical consequences of cisplatin chemotherapy are well-known, the precise mechanism of action remains elusive. Specific recognition of cisplatin-damaged DNA by a class of proteins containing the high-mobility group (HMG) domain DNA-binding motif could play a role in mediating the cytotoxicity of the drug. This study presents a quantitative investigation of binding of the murine testis-specific high-mobility group protein tsHMG to DNA modified by cisplatin. The binding affinity and specificity of this protein to a site-specific 1,2-d(GpG) cisplatin-DNA intrastrand cross-link in a 20 bp probe were determined. A value for the apparent dissociation constant, Kd(app), of 24 +/- 5 nM was obtained by gel mobility shift assays. Binding competition assays with the corresponding unmodified 20 bp probe gave a ratio (rho) of nonspecific to specific Kd(app) values of 230. A polypeptide containing tsHMG domain A (residues 1-82) was expressed and purified to homogeneity. This domain alone was sufficient for specific recognition of cisplatin-modified DNA with a Kd(app) of 300 +/- 50 nM and a rho of 20, a comparatively high discrimination factor. DNase I interference analysis of the adduct-containing strand revealed that tsHMG binding extends over 14 nucleotides, centered around the platinated bases. The domain A polypeptide protection pattern covers a slightly smaller area of 13 nucleotides. The binding affinity and specificity of tsHMG for cisplatin-modified DNA are exceptional compared to those of other HMG-domain proteins studied previously. The possible relevance of these findings to the mechanism of action of cisplatin is discussed.


The Politics of Prevention: Lessons from the Neglected History of US HIV/AIDS Policy.
The history of government action on HIV/AIDS has much to teach us about the dynamics and possibilities of US public health policy, but it has been insufficiently studied by social scientists of the epidemic. This article draws on a large set of original interviews with policy makers, thousands of news articles, and extensive documentation to reconstruct the history of three areas of debate and decision making about HIV prevention since 1990: needle exchange, HIV testing, and sex education for at-risk groups. These histories illuminate three key lessons. First, scientific evidence has less power to drive public health policy in the United States than in the United Kingdom, which is used as a comparison case to contextualize US choices within a broader range of options. Second, moral concerns weigh so heavily in the United States that a publicly articulated moral argument can countermand the dictates of solid scientific evidence, the voices of experts, and practical considerations to push public health policy in entirely oppositional directions. Third, having the ear of the presidential administration is usually a necessary-although not always sufficient-condition for the success of advocates trying to move US policy in the public health-indicated direction.


S. cerevisiae alpha pheromone receptors activate a novel signal transduction pathway for mating partner discrimination.
Wild-type S. cerevisiae cells of both mating types prefer partners producing high levels of pheromone and mate very infrequently to cells producing no pheromone. However, some mutants that are supersensitive to pheromone lack this ability to discriminate. In this study, we provide evidence for a novel role of alpha pheromone receptors in mating partner discrimination that is independent of the known G protein-mediated signal transduction pathway. Furthermore, in response to pheromone, receptors become localized to the emerging region of morphogenesis that is positioned adjacent to the nucleus, suggesting that receptor localization may be involved in mating partner discrimination. Actin, myosin 2, and clathrin heavy chain are involved in mating partner discrimination, since strains carrying mutations in the genes encoding these proteins result in a small but significant defect in mating partner discrimination.


The use of electrolyzed solutions for the cleaning and disinfecting of dialyzers.
Recently, the use of electrolyzed solutions has attracted considerable interest in Japan. This study investigates the efficiency of electrolyzed solutions as disinfecting agents (DA) in the reuse of dialyzers and compares their efficiency to that of other disinfectants currently in use. The following 3 methods were employed. First, the rinsing time and rebound release of reused dialyzers were measured and compared after electrolyzed solutions, electrolyzed strong acid aqueous solution (ESAAS) and electrolyzed strong basic aqueous solution (ESBAS), made from reverse osmosis (RO) water (ESAAS, ESBAS; Generating apparatuses: Super Oxseed alpha 1000, Amano Corporation, Yokohama, Japan), 2% Dialox-cj (Teijin Gambro Medical, Tokyo, Japan), and 3.8% formalin were used as DAs. This involved performing dialysis with 2 types of dialyzers: a cellulose acetate membrane (CAM) dialyzer and a polysulfone membrane (PSM) dialyzer. The dialyzers were cleaned and disinfected using the different DA and left for 48 h. Next, after performing dialysis the dialyzer membranes were cleaned with a saline solution (0.9% NaCl) and RO water and then cleaned with the various DA. These membranes were observed using a scanning electron microscope (SEM) to check for the presence of physical and biological contaminants. Finally, in vitro tests were performed to determine the level of dialyzer clearance when PSM dialyzers were reused after having been cleaned and disinfected with the electrolyzed solutions. The rinsing time results for both the CAM and PSM dialyzers showed the electrolyzed solutions (ESBAS and ESAAS) as being undetectable within 10 min. With regard to the rebound release, for both the CAM and PSM dialyzers, the electrolyzed solutions were undetectable at all checking times between 30 and 240 min. Observation by SEM showed that cleaning with both ESAAS and ESBAS left the fewest contaminants, and cleaning with 2% Dialox-cj left the highest level of contaminants in the CAM dialyzers. With regard to experiments concerning use in vitro, no major changes in the dialyzer clearance were noticed after 6 uses. In every experiment, the previous investigations showed the electrolyzed solutions to be superior to 3. 8% formalin and 2% Dialox-cj DA for the reuse of dialyzers.


Equine laryngeal hemiplegia part II: Some clinical observations.
Some clinical features of laryngeal hemiplegia in 127 horses are described. Possible aetiologic factors were found in only 11% of affected animals. The onset of clinical signs was either sudden or insidious. The majority of cases were presented because of an abnormal respiratory noise made at exercise. Other clinical signs, particularly those usually attributed to laryngopalatal dislocation, were observed in a substantial proportion of affected animals. In all cases surveyed the left arytenoid was affected, although in 3 animals a bilateral laryngeal dysfunction was noted. Thirty of 65 animals examined with a fibreoptic endoscope had other upper respiratory tract abnormalities in addition to abnormal arytenoid movements. Electrocardiographic examination of 45 affected horses did not reveal a significantly higher incidence of abnormalities than that observed in the racing population. The majority of haemograms taken from affected animals were also within normal limits.


Action of cytogenin on lymphoid cells and their cytokine production.
Action of cytogenin on macrophages and T cells was investigated. Phagocytosis of yeast and production of PMA-elicited superoxide anion by macrophages taken from mice given cytogenin po were augmented. Cytogenin enhanced productions of IL-1 alpha by macrophages and IFN gamma and GM-CSF by spleen cells although it did not enhanced production of TNF alpha by macrophages and IL-6 by macrophages and spleen cells. Macrophages stimulated with cytogenin caused to stimulate proliferation of purified T cells in Intercell cultures in which each cell population was cultured without contact. Results suggest that cytogenin primarily activates macrophages to produce monokines such as IL-1 alpha and it causes to stimulate proliferation and differentiation of T cells resulting in production of lymphokines such as IFN gamma and GM-CSF.


Rotational atherectomy in very long lesions: Results for the ROTATE registry.
Rotational atherectomy (RA) is relatively contraindicated in patients with lesions ≥25 mm of length. Aim of this study was to evaluate RA safety and efficacy in this subset of patients with new technology and devices. From April 2002 to August 2013, the ROTATE registry included all consecutive patients undergoing RA in 8 centres. They were divided into shorter lesion group (SLG, lesions < 25 mm) and longer lesion group (LLG, lesions ≥ 25 mm). The angiographic success (AS) was the primary end point. Procedural complications (PC), a composite end point of procedural perforation, slow flow/no flow, and in-hospital major acute cardiovascular events (MACE), were secondary end points, along with death, nonfatal MI, target lesion revascularization, and MACE during follow-up. Sensitivity analysis was performed according to generation of DES. 1186 patients were included: 51.5% in SLG and 48.4% in LLG. Mean age was 70.4 ± 9.3 years, 64.5% were male. AS and PC did not differ between the two groups (93% vs 91%, p = 0.24 and 9.8 vs 9.4%, p = 0.84). During follow-up (27.6 ± 22.9 months), MACE did not differ between the two groups (28% vs 29.1%, p = 0.95). At multivariate analysis chronic kidney disease, male gender increased risk of MACE (HR 1.94, IQR 1.29-2.0, p = 0.01, HR 0.52, IQR 0.34-0.79, p = 0.01) while second-generation DES seemed protective (HR 0.53, IQR 0.31-0.88, p = 0.02). Data were confirmed at sensitivity analysis for second-generation DES (759 pts, 63.9%). No differences were found in this subpopulation between the two groups in term of AS, PC, and long-term MACE (93.6% vs 93.5%, p = 0.28, 11.9% vs 9.4%, p = 0.32 and 25.5% vs 23.9%, p = 0.72, respectively). Treating coronary lesions ≥ 25 mm length with RA does not impact short- and long-term outcome, in particular, in patients with second-generation DES. © 2016 Wiley Periodicals, Inc.


Nonadhesive organ culture of human exocrine pancreatic cells with their stroma.
Studies using explanted tissue have shown that it is possible to keep adult human cells in organ culture with a preserved morphology for up to 1 month as spheres in a nonadhesive organ culture. The current study was to determine whether human exocrine pancreatic cells also can be grown in this manner. Small tissue samples from organ donors and tumor-free resection rim from patients with pancreatic carcinoma were obtained (n = 16 adults). From each patient, fragments of approximately 300 microm in diameter were cultured and investigated with light microscopy and scanning and transmission electron microscopy at the time of explantation and after 5, 10, 20, 30, and 40 days of culture. Incubation of cultured fragments with vital dyes revealed a viable epithelium. At the time of explantation all the tissue fragments had a rough appearance with an uneven, torn periphery. During the first week of culture the fragments became rounder, with a smooth surface covering the whole circumference. This spheroid morphology persisted for the rest of the 6-week culture period. The fragments were within 1 week covered by a highly differentiated, polarized epithelium with secretory apparatus, apical secretion granules, and microvilli, as well as specialized cell junctions, with the same appearance as acinoductal pancreatic cells of the original tissue. The core of the fragments consisted of connective tissue with vascular elements, fibroblasts, leukocytes, and a few ductal and acinar elements. Transmission electron microscopy of the spheroids revealed a continuous basal lamina underneath the epithelium. Immunostaining for cytokeratin 5, 6, 7, 8, 17, and 18 was strongly positive in the epithelium. These results show that normal exocrine pancreatic cells can be grown in vitro in a nonadhesive organ culture with their stroma.


Thiol/disulfide exchange is a prerequisite for CXCR4-tropic HIV-1 envelope-mediated T-cell fusion during viral entry.
Attachment of gp120 to CD4 during HIV-1 entry triggers structural rearrangement in gp120 that enables binding to an appropriate coreceptor. Following coreceptor engagement, additional conformational changes occur in the envelope (Env), resulting in fusion of virion and cell membranes. Catalysts with redox-isomerase activity, such as protein disulfide isomerase (PDI), facilitate Env conversion from its inactive to its fusion-competent conformation. We report here that anti-PDI agents effectively block CXCR4 Env-mediated fusion and spread of virus infection. Exogenously added PDI, in turn, can rescue fusion from this blockade. We further find that PDI facilitates thiol/disulfide rearrangement in gp120 during conformational change, whereas inhibition of this redox shuffling prevents gp41 from assuming the fusogenic 6-helix bundle conformation. At the virus-cell contact site, gp120 induces assembly of PDI, CD4, and CXCR4 into a tetramolecular protein complex serving as a portal for viral entry. Our findings support the hypothesis that Env conformational change depends on a well-coordinated action of a tripartite system in which PDI works in concert with the receptor and the coreceptor to effectively lower the activation energy barrier required for Env conformational rearrangement.


A PNA-mediated clamping PCR for routine detection of KRAS mutations in colorectal carcinoma.
The detection of somatic mutations in a tumor represents a valuable tool for tumor characterization and provides the clinicians with information for setting up the most appropriate therapy. KRAS mutations in codons 12 and 13 are important biomarkers routinely analyzed in the clinic for the management of anti-EGFR treatment in colorectal carcinoma (CRC). Here we report a sensitive and inexpensive assay for KRAS mutations based on a PNA-mediated PCR clamping. The assay displays very high sensitivity (0.7%) and specificity (96.7%) when compared to traditional sequencing (SS) and pyrosequencing (PS), two of the most commonly and routinely used methods employed today by diagnostic laboratories. Furthermore, the PNA assay requires only basic and low-cost laboratory equipment, in contrast with all the most recent PCR-based technologies, which are highly sensitive but also much more expensive. Finally, despite the PNA assay does not allow for the definition of specific mutations, it is the cheapest and easiest screening method to firstly stratify wild-type and mutated patients, information that is strictly necessary to clinicians for the management of CRC and anti-EGFR treatment.


High serum nerve growth factor concentrations are associated with good functional outcome at 3 months following acute ischemic stroke.
Previous studies in animal model have demonstrated that neurotrophins were associated with functional outcome following stroke. However, the relationship between serum nerve growth factor (NGF) and functional outcome in stroke patients has not been explored. Our objective was to investigate the association between serum NGF concentrations at admission and functional outcome of patients at 3 month after stroke. One-hundred eight-five patients with acute ischaemic stroke were recruited in our study. Serum NGF concentrations were measured by ELISA at admission. The stroke severity at admission was assessed by the National Institute of Health Stroke Scale (NIHSS). The modified Rankin Scale (mRS) was used to assess the functional outcome of patients at 3 month after stroke. In addition, 100 healthy controls were recruited. Serum NGF concentrations were higher in good functional outcome group (mRS score of 0-2) than that in poor functional outcome group (mRS score of 3-6) (9.51 ± 2.33 vs. 8.12 ± 1.61, P < 0.001). Meanwhile, the serum NGF concentrations in healthy group were lower than that in acute ischemic stroke patients (7.17 ± 1.49 vs. 9.15 ± 2.24, P < 0.001). Moreover, our results demonstrated that high serum NGF concentrations (>9.21 ng/l) were independently associated with the better functional prognosis at 3 months following the occurrence of stroke (OR 0.048, 95% CI 0.012-0.185, P < 0.001). High concentrations of serum NGF at admission may predict good functional outcome of patients at 3 months after acute cerebral ischemia stroke.


Cyclic nucleotide involvement in histamine release from mast cells--a reevaluation.
Secretory events in cells in general are accompanied by increased levels of cyclic AMP. In mast cells, however, the pattern is reversed. Thus histamine release is associated with a fall in cAMP. It has been suggested that the lowered levels of cAMP lead to an increase in membrane permeability towards calcium and that an influx of such ions triggers the release mechanisms. It has further been reported that high levels of cAMP inhibit histamine release by decreasing the permeability. However, evidence has now accumulated indicating that this general concept is far too simplistic. Studies are reviewed which imply that there is little or no correlation between histamine release and intracellular levels of cyclic nucleotides. A new working hypothesis with respect to the role of these nucleotides in mast cell secretion is proposed.


[Preservation of teeth in elderly persons].
Conservative dentistry by elder people has regard to the physiological changes during the function. There is no limitation of conservative dentistry conditional by the old age.


Interaction between blood flow and motility in normal and inflamed ileum.
The alterations in local and superior mesenteric blood flow during ileal inflammation and their correlations with motility in the normal and the inflamed ileum were investigated in the conscious state. Ileal inflammation decreased the local mesenteric blood flow but had no significant effect on the superior mesenteric blood flow. A significant reduction or an increase in local mesenteric blood flow in the normal or the inflamed ileum had no effect on local contractile activity. The vascular reactivity to vaso-dilators and vaso-constrictors was significantly reduced during inflammation. Local mesenteric blood flow increased significantly in the descending segment ahead of a caudal propagating giant migrating contraction. The local mesenteric blood flow oscillated during a migrating motor complex (MMC) cycle. We conclude that a several-fold increase or decrease in local mesenteric blood flow lasting for several minutes does not affect contractility. Ileal inflammation decreases local mesenteric blood flow but does not affect the total blood flow to the small intestine.


The role of IgE in childhood asthma.
The influence of age and sex has been in 208 asthmatic children on the basis of the following parameters: total serum IgE concentration (RIST), serum concentration of specific IgE antibodies (RAST), and positive prick tests against Dermatophagoides Pleronissynus, grasses, and Alternaria Tenuis. The results indicate that all these parameters are significantly influenced by age. Arithmetic values for RIST show a significant difference between the sexes which is obscured by logarithmic calculation. The data strongly suggest that IgE antibodies cannot be considered the main mechanism by which asthma is produced in small children.


Long-term kidney graft survival.
1. More than 90% of long-term grafts were first transplants. 2. The percentage of long-term transplants from living-related donors decreased from 78% in the years prior to 1968 to 42% in the 1973-1977 period. 3. More than 60% of living-related long-term grafts were from sibling donors. 4. Among long-term survivors, there was no difference from the expected rates in the percentage of red blood cell groups. 5. HLA-A,B matching resulted in significant improvement in graft survival rates for both cadaver donor and related transplants.


Hypothalamo-pituitary-adrenal axis in patients with prostatic carcinoma.
Insulin-induced pituitary growth hormone (GH), adrenocorticotrophic hormone (ACTH) and adrenal cortical response were studied in 12 patients with prostatic carcinoma. 3 patients demonstrated significant abnormal GH release associated with concentrations which remained on a high plateau during the study. 5 patients showed lack of ACTH-cortisol response to insulin-induced hypoglycemia. Those patients subsequently presented clinically with rapidly progressing disease.


Where are we with the management of hypertension? From science to clinical practice.
The management of elevated blood pressure in patients at high cardiovascular risk is still a subject of debate. The authors review current international guidelines and results of large clinical trials and recent meta-analyses to discuss the different approaches in patients at high risk for cardiovascular events. The different treatment options are considered in view of the modern approach and of the different classes of drugs (diuretics, angiotensin-converting enzyme inhibitors, calcium channel blockers, beta-blockers, and angiotensin II receptor blockers) currently in use. A case report is presented as an illustration of the difficulties related to the management of high blood pressure in patients at increased risk. The benefits of the use of 2 medications that include an inhibitor of the renin-angiotensin-aldosterone system and a calcium channel blocker or a diuretic are discussed. Choosing the proper drugs and correct doses are important considerations for the long-term management of hypertension.


Lignin degradation in a compost environment by the deuteromycete Paecilomyces inflatus.
Two strains of the deuteromycete Paecilomyces inflatus were isolated from compost samples consisting of municipal wastes, paper and wood chips. Lignin degradation by P. inflatus was studied following the mineralization of a synthetic (14)C(beta)-labeled lignin (side-chain labeled dehydrogenation polymer, DHP). Approximately 6.5% of the synthetic lignin was mineralized during solid-state cultivation of the fungus in autoclaved compost; and 15.5% was converted into water-soluble fragments. Laccase was the only ligninolytic enzyme detectable when the isolates were grown in autoclaved compost. Production of the enzyme was growth-associated and dependent on the culture conditions. The optimal pH for laccase production was between 4.5 and 5.5 and the optimal temperature was around 30 degrees C. Activity levels of laccase increased in the presence of low-molecular-mass aromatic compounds, such as veratryl alcohol, veratric acid, vanillin and vanillic acid.


Simultaneous inactivation of the catalytic activities of yeast glutathione reductase by N-alkylmaleimides.
A series of straight chain N-alkymaleimides was shown to simultaneously inactivate the reductase, transhydrogenase and diaphorase activities of yeast glutathione reductase (NAD(P)H: oxidized-glutathione oxidoreductase, EC 1.6.4.2.) at pH 7.5 and 25 degrees C. Apparent second-order rate constants for the inactivation of all enzyme activities exhibited parallel increases with increasing chainlength from C-2 through C-7 of the alkyl substituent of the enhanced binding of maleimides through nonpolar interactions with the enzyme. Reduction of the active site disulfide with NADPH was required prior to addition of maleimide for inactivation to occur. NADP, AcPyADP, SNADP, AADP, and oxidized glutathione all protected the enzyme from inactivation. 2'AMP, 3' AMP, 2'-phospho-5' AMP, 2'-phospho5'-ADP and 2'-phospho-ADP-ribose although all coenzyme-competitive inhibitors failed to protect the enzyme from N-ethylmaleimide inactivation. N-Phenyl and N-alkylmaleimides covalently modified two, of six available sulfhydryl groups per subunit. No other amino acid residues were modified. The reactivity of these sulfhydryl groups was at least two orders of magnitude higher than any reported for the N-ethylmaleimide reaction with many other 'essential sulfhydryl' enzymes. No change in the charge transfer band of the reduced enzyme was observed upon complete inactivation by N-ethyl, N-heptyl or N-phenylmaleimide. The retention of the charge transfer band after selective modification of two sulfhydryl groups suggests the involvement of a third reactive sulfhydryl group in the functioning of the yeast enzyme. No inactivation was observed when coenzymatically reduced enzyme was incubated with the site-specific sulfhydryl reagent, diazotized AADP.


Implementing the Mental Health Act 2007 in British general practice: Lessons from Ireland.
Changes in mental health legislation (e.g. Mental Health Act 2007 in England and Wales, Mental Health Act 2001 in Ireland) have generally improved adherence to international human rights standards, but also present challenges to primary care providers. When mental health legislation was substantially reformed in Ireland, 62.9% of general practitioners (GPs) felt the new legislation was not user-friendly. Majorities of GPs who felt the legislation affected their practice reported increased workloads (85%) and various other difficulties (53%). GPs who had received training about the legislation were more likely to find it user-friendly (43% versus 30.9%), and informal training (e.g. from colleagues) was just as likely as formal training to be associated with a GP finding it user-friendly. With similar changes to mental health legislation being introduced in England and Wales, it is significant that informal training is just as good as formal training in helping GPs work with new mental health legislation.


Toll-like receptors: from the discovery of NFkappaB to new insights into transcriptional regulations in innate immunity.
Toll-like receptors (TLRs) are key components of the innate immune system, functioning as pattern recognition receptors that recognise a wide range of microbial pathogens. TLRs represent a primary line of defence against invading pathogens in mammals, plants and insects. Recognition of microbial components by TLRs triggers a cascade of cellular signals that culminates in the activation of NFkappaB which leads to inflammatory gene expression and clearance of the infectious agent. The history of NFkappaB began with the TLR4 ligand lipopolysaccharide (LPS), a component of the cell wall of Gram-negative bacteria, since this was the stimulus first used to activate NFkappaB in pre-B-cells. However, since those early days it has been a circuitous route, made possible by drawing on information provided by many different fields, that has led us not only to the discovery of TLRs but also to an understanding of the complex pathways that lead from TLR ligation to NFkappaB activation. In this review we will summarize the current knowledge of TLR-mediated NFkappaB activation, and also the recent discoveries that subtle differences in kappaB binding sequences and NFkappaB dimer formation result in specific gene expression profiles.


Ten-year results of randomized trial comparing radiotherapy and concomitant bleomycin to radiotherapy alone in epidermoid carcinomas of the oropharynx: experience of the European Organization for Research and Treatment of Cancer.
This trial of treatment for head and neck carcinoma was initiated in 1973 by the European Organization for Research and Treatment of Cancer. Its purpose was to investigate the value of single-agent chemotherapy with bleomycin (BLM) given during the course of a conventional treatment by external radiotherapy (RT) compared to treatment by external RT alone. In this randomized study, we compared treatment results in 2 groups of patients with squamous cell carcinoma of the oropharynx (T2, T3, and T4; International Union Against Cancer classification). One group of 92 patients was treated by RT at the prescribed dose of 70 Gy. The other group of 107 patients received radiation according to the same protocol and simultaneously received im injection of BLM at a dose of 15 mg twice a week, 2 hours prior to the session of RT, for a total dose of 150 mg in 5 weeks. The occurrence of local toxic effects (i.e., mucositis and epidermatitis) was significantly greater in the RT-BLM group (RT-BLM, 72%, vs. RT, 21%). Primary tumor response 6 weeks after completion of RT was the same in both arms of the study (RT, 68%, vs. RT-BLM, 67%). The 6-year survival rate was 24% (RT-BLM) versus 22% (RT). Long-term analysis (10 yr) is given.


Experimental free-space optical network for massively parallel computers.
A free-space optical interconnection scheme is described for massively parallel processors based on the interconnection-cached network architecture. The optical network operates in a circuit-switching mode. Combined with a packet-switching operation among the circuit-switched optical channels, a high-bandwidth, low-latency network for massively parallel processing results. The design and assembly of a 64-channel experimental prototype is discussed, and operational results are presented.


Nonsurgical retrieval of an accidentally dislodged vent catheter retention ring.
During open mitral commissurotomy in a patient with mitral stenosis, a vent catheter retention ring was accidentally slipped off into the left atrium and lodged near the orifice of the right renal artery. Nonsurgical retrieval of this intraarterial foreign body was performed successfully under fluoroscopic guidance in the operating room using a combined approach of angiographic catheters and guidewire, these being inserted via the arteriotomy site of the right femoral artery created for cardiopulmonary bypass.


Calcite microneedle arrays produced by inorganic ion-assisted anisotropic dissolution of bulk calcite crystal.
Besides studies on the mineralization process, research on the demineralization of minerals provides another way to understand the crystallization mechanism of biominerals and fabricate crystals with complicated morphologies. The formation of ordered arrays of c-axis-oriented calcite microneedles with a tri-symmetric structure and lengths of more than 20 μm was realized on a large scale for the first time through anisotropic dissolution of calcite substrates in undersaturated aqueous solution in the presence of ammonium salts. The lengths and the aspect ratios of the calcite microneedles can be tuned by simply changing the concentrations of the ammonium salts and the dissolution time. The shape of the transverse cross sections of the calcite microneedles obtained in the presence of NH4 Cl and NH4 Ac is almost regularly triangular. The tri-symmetric transverse cross-section geometry of the calcite microneedles could be attributed to the tri-symmetric feature of rhombohedral calcite atomic structures, the synergetic interactions between electrostatic interaction of ammonium ions and dangling surface carbonate groups, and the ion incorporation of halide ions.


Global Health Diplomacy, "San Francisco Values," and HIV/AIDS: From the Local to the Global.
San Francisco has a distinguished history as a cosmopolitan, progressive, and international city, including extensive associations with global health. These circumstances have contributed to new, interdisciplinary scholarship in the field of global health diplomacy (GHD). In the present review, we describe the evolution and history of GHD at the practical and theoretical levels within the San Francisco medical community, trace related associations between the local and the global, and propose a range of potential opportunities for further development of this dynamic field. We provide a historical overview of the development of the "San Francisco Model" of collaborative, community-owned HIV/AIDS treatment and care programs as pioneered under the "Ward 86" paradigm of the 1980s. We traced the expansion and evolution of this model to the national level under the Ryan White Care Act, and internationally via the President's Emergency Plan for AIDS Relief. In parallel, we describe the evolution of global health diplomacy practices, from the local to the global, including the integration of GHD principles into intervention design to ensure social, political, and cultural acceptability and sensitivity. Global health programs, as informed by lessons learned from the San Francisco Model, are increasingly aligned with diplomatic principles and practices. This awareness has aided implementation, allowed policymakers to pursue related and progressive social and humanitarian issues in conjunction with medical responses, and elevated global health to the realm of "high politics." In the 21st century, the integration between diplomatic, medical, and global health practices will continue under "smart global health" and GHD paradigms. These approaches will enhance intervention cost-effectiveness by addressing and optimizing, in tandem with each other, a wide range of (health and non-health) foreign policy, diplomatic, security, and economic priorities in a synergistic manner--without sacrificing health outcomes.


17 beta-estradiol-BSA conjugates and 17 beta-estradiol regulate growth plate chondrocytes by common membrane associated mechanisms involving PKC dependent and independent signal transduction.
Nuclear receptors for 17 beta-estradiol (E(2)) are present in growth plate chondrocytes from both male and female rats and regulation of chondrocytes through these receptors has been studied for many years; however, recent studies indicate that an alternative pathway involving a membrane receptor may also be involved in the cell response. E(2) was found to directly affect the fluidity of chondrocyte membranes derived from female, but not male, rats. In addition, E(2) activates protein kinase C (PKC) in a nongenomic manner in female cells, and chelerythrine, a specific inhibitor of PKC, inhibits E(2)-dependent alkaline phosphatase activity and proteoglycan sulfation in these cells, indicating PKC is involved in the signal transduction mechanism. The aims of the present study were: (1) to examine the effect of a cell membrane-impermeable 17 beta-estradiol-bovine serum albumin conjugate (E(2)-BSA) on chondrocyte proliferation, differentiation, and matrix synthesis; (2) to determine the pathway that mediates the membrane effect of E(2)-BSA on PKC; and (3) to compare the action of E(2)-BSA to that of E(2). Confluent, fourth passage resting zone (RC) and growth zone (GC) chondrocytes from female rat costochondral cartilage were treated with 10(-9) to 10(-7) M E(2) or E(2)-BSA and changes in alkaline phosphatase specific activity, proteoglycan sulfation, and [(3)H]-thymidine incorporation measured. To examine the pathway of PKC activation, chondrocyte cultures were treated with E(2)-BSA in the presence or absence of GDP beta S (inhibitor of G-proteins), GTP gamma S (activator of G-proteins), U73122 or D609 (inhibitors of phospholipase C [PLC]), wortmannin (inhibitor of phospholipase D [PLD]) or LY294002 (inhibitor of phosphatidylinositol 3-kinase). E(2)-BSA mimicked the effects of E(2) on alkaline phosphatase specific activity and proteoglycan sulfation, causing dose-dependent increases in both RC and GC cell cultures. Both forms of estradiol inhibited [(3)H]-thymidine incorporation, and the effect was dose-dependent. E(2)-BSA caused time-dependent increases in PKC in RC and GC cells; effects were observed within three minutes in RC cells and within one minute in GC cells. Response to E(2) was more robust in RC cells, whereas in GC cells, E(2) and E(2)-BSA caused a comparable increase in PKC. GDP beta S inhibited the activation of PKC in E(2)-BSA-stimulated RC and GC cells. GTP gamma S increased PKC in E(2)-BSA-stimulated GC cells, but had no effect in E(2)-BSA-stimulated RC cells. The phosphatidylinositol-specific PLC inhibitor U73122 blocked E(2)-BSA-stimulated PKC activity in both RC and GC cells, whereas the phosphatidylcholine-specific PLC inhibitor D609 had no effect. Neither the PLD inhibitor wortmannin nor the phosphatidylinositol 3-kinase inhibitor LY294022 had any effect on E(2)-BSA-stimulated PKC activity in either RC or GC cells. The classical estrogen receptor antagonist ICI 182780 was unable to block the stimulatory effect of E(2)-BSA on PKC. Moreover, the classical receptor agonist diethylstilbestrol (DES) had no effect on PKC, nor did it alter the stimulatory effect of E(2)-BSA. The specificity of the membrane response to E(2) was also demonstrated by showing that the membrane receptor for 1 alpha,25-(OH)(2)D(3) was not involved. These data indicate that the rapid nongenomic effect of E(2)-BSA on PKC activity in RC and GC cells is dependent on G-protein-coupled PLC and support the hypothesis that many of the effects of E(2) involve membrane-associated mechanisms independent of classical estrogen receptors. (c) 2001 Wiley-Liss, Inc.


Impact of diabetes education and self-management on the quality of care for people with type 1 diabetes mellitus in the Middle East (the International Diabetes Mellitus Practices Study, IDMPS).
Self-management (self-monitoring of blood glucose, plus self-adjustment of insulin dose) is important in diabetes care, but its complexity presents a barrier to wider implementation, which hinders attainment and maintenance of glycemic targets. More evidence on self-management is needed to increase its implementation and improve metabolic outcomes. Data from 1316 participants with type 1 diabetes mellitus who were enrolled from Middle East countries into the International Diabetes Management Practices Study (IDMPS), a multinational observational survey, were analyzed to assess the impact of education on disease management and outcomes. A majority (78%) of participants failed to achieve glycemic target (HbA1c < 7.0% [<53 mmol/mol]). Participants who had received diabetes education (59%) were more likely to practice self-management than those who had not (odds ratio [OR]: 2.51; 95% confidence interval [CI]: 1.7-3.69; p < 0.001), and those who practiced self-management were more likely to attain target HbA1c than those who did not (OR: 1.49; 95% CI: 1.06-2.09; p = 0.023). These relationships between diabetes education, self-management and glycemic control suggest that diabetes education provides knowledge and skills to optimize self-management, favoring HbA1c target attainment. Middle East health authorities should search for ways to facilitate access to diabetes education to optimize treatment outcomes.


A special report: histocompatibility testing guidelines for hematopoietic stem cell transplantation using volunteer donors.
The World Marrow Donor Association has formulated guidelines for establishing the extent and quality of histocompatibility testing for unrelated donor registries, umbilical cord blood banks, and transplant centers involved in international exchange of hematopoietic stem cells for allogeneic transplantation. Registry and cord blood bank guidelines suggest that, at a minimum, initial HLA typing should be performed for three HLA loci, HLA-A, -B, and -DR, at low resolution/split antigen level. DNA-based testing methods should be utilized for HLA-DR typing. DNA-based testing for HLA-A and -B should replace serologic testing of new volunteer donors and cord blood units as robust protocols and reagents become available to the laboratories. Transplant center guidelines for typing of patient, family and to confirm the HLA types of potential unrelated donors should include, at the minimum, typing HLA-A, B, and -DR loci using primarily DNA-based testing methods at allele level resolution for DRB1 and low resolution/ split antigen level for HLA-A and -B. It is strongly recommended that the typing of a patient and the selected donor be performed using the same set of reagents, methodology, and interpretation criteria with fresh tissue samples to ensure HLA identity. Guidelines for laboratory accreditation, approaches to quality assurance and quality control for HLA testing, and suggestions for the format of the HLA database of donor types are also outlined.


Syntheses of selectively fluorinated cyclodecenones: the first deployment of the neutral oxy-Cope rearrangement in organofluorine chemistry.
Metallated haloalkenes were used to open epoxides in moderate to good yield. The homoallylic alcohols obtained underwent Swern oxidation to afford three gamma,gamma-difluorinated beta,gamma-enones, which reacted with either vinyllithium,2-lithio-2H-dihydropyran or another metallated haloalkene to afford substituted trans-1,2-divinylcyclohexanols of different degrees of stability. These intermediates underwent neutral thermal oxy-Cope rearrangements when heated in xylene in Ace tubes. The first-formed enols ketonised without loss of HF to afford a range of cyclodecenones in moderate to good yield; X-ray crystallography was used extensively for product characterisation. All substrates rearranged more rapidly than a cis/trans mixture of 1,2-divinylcyclohexanols.


A selective voltammetric method for uric acid detection at beta-cyclodextrin modified electrode incorporating carbon nanotubes.
A beta-cyclodextrin-coated electrode incorporating carbon nanotubes was constructed and applied to the detection of uric acid in the presence of high concentration of ascorbic acid. The major obstacle of the overlapped oxidation potential of ascorbic acid was overcome owing to the distinct ability of the carbon nanotubes-modified electrode to yield a large anodic peak difference ca. 400 mV. The sensitive detection of uric acid has been further improved by the formation of a supramolecular complex between beta-cyclodextrin and uric acid. A linear calibration curve was obtained for 5 x 10(-7) to 5 x 10(-5) M in 0.2 M HAc-NaAc buffer (pH 4.5) with correlation coefficient of 0.998 and detection limit of 0.2 microM. The practical analytical application was illustrated by a selective measurement of uric acid in human urine without any preliminary treatment.


The Lay Advocates' Communication Assessment Tool (LACAT).
A tool to assess communication strategies used by lay advocates was developed and tested with 96 Latina and Caucasian study participants who were invited to promote a prevention trial to other women. Subscales showed strong initial reliability estimates and included: (a) telling personal stories, (b) describing the benefits of participation, (c) expressing caring, (d) emphasizing future generations' health, (e) repeating the message, and (e) communicating the importance of the study to one's own ethnic group. The subscales that comprise the Lay Advocacy Communication Assessment Tool may serve as a basis for developing a validated instrument and may subsequently be used to identify effective recruitment strategies.


A valley valve and electron beam splitter.
Developing alternative paradigms of electronics beyond silicon technology requires the exploration of fundamentally new physical mechanisms, such as the valley-specific phenomena in hexagonal two-dimensional materials. We realize ballistic valley Hall kink states in bilayer graphene and demonstrate gate-controlled current transmission in a four-kink router device. The operations of a waveguide, a valve, and a tunable electron beam splitter are demonstrated. The valley valve exploits the valley-momentum locking of the kink states and reaches an on/off ratio of 8 at zero magnetic field. A magnetic field enables a full-range tunable coherent beam splitter. These results pave a path to building a scalable, coherent quantum transportation network based on the kink states.


Health problems of the population in different regions of the Ukraine.
The ecological situation in some regions of the Ukraine is critical due to the concentration of major ferrous and nonferrous metallurgy, oil refining and chemical industries, and due to the consequences of the Chernobyl accident. The health status of the whole population over the last few years has deteriorated and resulted in 1992 in a decrease in the birth-rate coefficient to 11.5 per million and an increase in the mortality rate up to 13.4 per million. The average level of life expectancy for men and women in 1991 decreased to 63.3 and 74.5 years, respectively. In 1991 the number of occupational diseases registered increased to 7958 or 3 per 10,000 of the working population, which does not reflect the real situation in the country. Major medical and biological problems of the consequences of the Chernobyl accident are restricted to the field of studying the effect of low-dose exposure and assessment of delayed stochastic effects. Until now no significant increase was registered in age-adjusted cancer, leukemia and lymphoma incidence rates among the male and female population of the most contaminated, strictly controlled territories and regions of the Ukraine in comparison with the average rate in the whole country. But the incidence of thyroid cancer in 1990 was 0.23, in 1991 0.19 and in 1992 0.35 per 100,000 children under 14 years of age. In the Ukraine the incidence of thyroid cancer in 1981-1985 did not exceed 0.04-0.06 cases per 100,000 children.


Clinical consequences and management of hypomagnesemia.
Magnesium deficiency and hypomagnesemia remain quite prevalent, particularly in patients in intensive care units, and may have important clinical consequences. Magnesium should be measured directly in clinical circumstances in which a risk for magnesium deficiency exists and appropriately corrected when found. This commentary reviews the current knowledge of magnesium homeostasis and the risk factors and clinical consequences of magnesium deficiency and outlines approaches to therapy.


Isolation of a pure toxic polypeptide from the venom of the spider Phoneutria nigriventer and its neurophysiological activity on an insect femur preparation.
The venom of the South American spider Phoneutria nigriventer has been separated into eleven fractions by gel filtration. The neurophysiological activity of each fraction was tested by perfusion of a locust femur preparation. Fractions which gave a neurophysiological response on this perfusion were fractionated further by ion-exchange chromatography. The purity of each sub-fraction was monitored by isoelectrofocusing on polyacrylamide gels and isoelectric points determined. From one of the polypeptide-containing fractions, a pure, almost neutral polypeptide was isolated and shown to have a molecular weight between 5500 and 5900. The amino acid composition of the pure polypeptide was: Ala6,7 Arg2,3 Asx3 Cys8 Glx3 Gly4 Ile4 Leu1 Lys5,6 Phe2 Ser5 Thr3 Trp1 Tyr2 Val2. This polypeptide elicited the greatest neurophysiological activity of all fractions tested. When the polypeptide (2 X 10(-7) M) was perfused through the locust femur preparation, action potentials were generated along the length of the axons in the crural nerve, resulting in very rapid and uncontrolled twitching of the skeletal muscles. At higher concentrations, the crural nerve discharged repetitively, both spontaneously and in response to a single electrical stimulus. The other polypeptide fractions, although less pure, had neurophysiological responses similar to those observed with the pure polypeptide; the effects of some fractions could be reversed. Further fractions of low molecular weight were purified by thin-layer or paper chromatography to give two pure components that are probably nucleosides or nucleotides. After the initial gel filtration of the total venom had separated the high molecular weight proteinases from the polypeptides, all of the polypeptides retained their neurophysiological activity in solution for several days. In the presence of the proteinases, the polypeptides were inactivated in solution in a few hours at room temperature.


Treatment of endemic mycoses.
The endemic mycoses are a diverse group of diseases caused by thermally dimorphic fungi. While they share many characteristics, each has unique aspects with regards to their clinical course, diagnosis and management. Diagnosis may be difficult and delayed owing to the varied manifestations and wide differential diagnosis. Historically, treatment has been with amphotericin B, which has been limited by its significant toxicity. The advent of the azole class of medications has allowed for safer alternatives to amphotericin B. The azoles have become the mainstay of treatment for many, if not most, forms of these diseases. Guidelines have been released for the management of each of the North American endemic mycoses; however, many questions remain as to the best strategies for the diagnosis and management of various manifestations of these diseases.


Effects of hydration on febrile temperature patterns in rabbits.
Patients with fever have a predisposition to experience dehydration, which may alter their thermoregulatory responses to elevated body temperature. In view of the recent discovery of the antipyretic activity of arginine vasopressin (AVP), it is possible that dehydration has a beneficial role during fever. Dehydration may enhance endogenous antipyresis by stimulating AVP release, making aggressive fluid replacement, which may inhibit AVP release, undesirable during fever. This study addressed the effects of manipulation of hydration status on temperature and cardiovascular responses in endotoxin-injected rabbits. Eight unanesthetized chronically instrumented rabbits were exposed to lipopolysaccharide (LPS) while in euhydrated state, after furosemide (5 mg/kg) and 24 hours of water deprivation (dehydrated), after infusion of saline (30 mL/kg) while in euhydrated state (hyperhydrated), and after saline (mL/per overnight body weight loss in grams) while in dehydrated state (rehydrated). Dehydrated rabbits display higher fevers that are biphasic in nature and are accompanied by increased vasoconstriction and duration of mean arterial pressure increases, indicating that activation of antipyretic mechanisms in dehydrated rabbits was not sufficient to reduce body core temperature. In addition, fluid supplementation in euhydrated rabbits did not alter the febrile response; however, a marked decrease in heart rate was noted. Furthermore, fluid supplementation in dehydrated rabbits significantly attenuates the rectal temperature and heart rate response to LPS injection, indicating the possibility that activation of antipyretic mechanisms of AVP in rehydrated rabbits was sufficient to reduce body core temperature. The results suggest that fluid supplementation has a beneficial role in keeping body temperature lower .


Inflammatory pseudotumor of the liver--another case report. Is this the beginning of an established hepatic entity?
Inflammatory pseudotumor of the liver is an infrequent, fibroinflammatory non-neoplastic process of unknown etiology, generally following a benign inflammatory condition. The importance of knowledge of it resides in its similar presentation to other hepatic tumors in clinical picture, radiological appearance, and macroscopic pattern. A 71-year-old woman presented with acute abdominal pain. Ultrasonography and a computerized tomography (CT) scan showed a 3.2 cm hepatic tumor (segment IV) and a CT-guided liver biopsy revealed possible histological features of hepatic fibrosarcoma. The patient underwent a wedge resection. The pathologist identified a well-defined, 4-cm inflammatory pseudotumor of the liver associated with possible sclerosing cholangitis lesion. Inflammatory pseudotumor is a fibroinflammatory non-neoplastic process that should be suspected in patients with a hepatic tumor with significant infectious-inflammatory history. Percutaneous hepatic biopsy does not provide certainty in confirming the lesion since it does not discard focuses of hidden malignancy. The treatment is surgical resection followed by histopatological study to eliminate a hepatocarcinoma, a low-grade fibrosarcoma, or a hidden focus of adenocarcinoma. The inflammatory pseudotumor of the liver has changed from being an extremely rare pathology to becoming an established liver disease.


Doping silicon nanocrystals and quantum dots.
The ability to incorporate a dopant element into silicon nanocrystals (NC) and quantum dots (QD) is one of the key technical challenges for the use of these materials in a number of optoelectronic applications. Unlike doping of traditional bulk semiconductor materials, the location of the doping element can be either within the crystal lattice (c-doping), on the surface (s-doping) or within the surrounding matrix (m-doping). A review of the various synthetic strategies for doping silicon NCs and QDs is presented, concentrating on the efficacy of the synthetic routes, both in situ and post synthesis, with regard to the structural location of the dopant and the doping level. Methods that have been applied to the characterization of doped NCs and QDs are summarized with regard to the information that is obtained, in particular to provide researchers with a guide to the suitable techniques for determining dopant concentration and location, as well as electronic and photonic effectiveness of the dopant.


GABA representation in hypoxia sensing: a ventilatory study in the rat.
Phenibut, a nonspecific GABA derivative, is clinically used as an anxiolytic and tranquilizer in psychosomatic conditions. A GABA-ergic inhibitory pathway is engaged in respiratory control at both central and peripheral levels. However, the potential of phenibut to affect the O2-related chemoreflexes has not yet been studied. In this study we seek to determine the ventilatory responses to changes in inspired O2 content in anesthetized, spontaneously-breathing rats. Steady-state 5-min responses to 10% O2 in N2 and 100% O2 were taken in each animal before and 1 h after phenibut administration in a dose 450 mg/kg, i.p. Minute ventilation and its frequency and tidal components were obtained from the respiratory flow signal. We found that after a period of irregular extension of the respiratory cycle, phenibut stabilized resting ventilation at a lower level [20.0±3.3 (SD) vs 31.1±5.2 ml/min before phenibut; P<0.01]. The ventilatory depressant effect of phenibut was not reflected in the hypoxic response. In relative terms, this response was actually accentuated after phenibut; the peak hypoxic ventilation increased by 164% from baseline vs the 100% increase before phenibut. Regarding hyperoxia, its inhibitory effect on breathing was more expressed after phenibut. In conclusion, the GABA-mimetic phenibut did not curtail hypoxic ventilatory responsiveness, despite the presence of GABA-ergic pathways in both central and peripheral, carotid body mechanisms mediating the hypoxic chemoreflex. Thus, GABA-mediated synaptic inhibition may be elaborated in a way to sustain the primarily defensive ventilatory chemoreflex.


Validation list no. 113. List of new names and new combinations previously effectively, but not validly, published.
The purpose of this announcement is to effect the valid publication of the following new names and new combinations under the procedure described in the Bacteriological Code (1990 Revision). Authors and other individuals wishing to have new names and/or combinations included in future lists should send three copies of the pertinent reprint or photocopies thereof, or an electronic copy of the published paper, to the IJSEM Editorial Office for confirmation that all of the other requirements for valid publication have been met. It is also a requirement of IJSEM and the ICSP that authors of new species, new subspecies and new combinations provide evidence that types are deposited in two recognized culture collections in two different countries (i.e. documents certifying deposition and availability of type strains). It should be noted that the date of valid publication of these new names and combinations is the date of publication of this list, not the date of the original publication of the names and combinations. The authors of the new names and combinations are as given below, and these authors' names will be included in the author index of the present issue and in the volume author index. Inclusion of a name on these lists validates the publication of the name and thereby makes it available in bacteriological nomenclature. The inclusion of a name on this list is not to be construed as taxonomic acceptance of the taxon to which the name is applied. Indeed, some of these names may, in time, be shown to be synonyms, or the organisms may be transferred to another genus, thus necessitating the creation of a new combination.


HLA-DQA1, DQB1 and DPB1 alleles on HLA-DQ2- and DQ9-carrying extended haplotypes.
DQA1, DQB1 and DPB1 alleles were investigated in a large panel of samples carrying HLA-DQ2- and HLA-DQ9-bearing extended haplotypes. Every instance of the [HLA-B8, SCO1, DR3, DQ2a] and [HLA-B18, F1C30, DR3, DQ2b] extended haplotypes carried the DQA1*0501 allele, while every instance of [HLA-B44, FC31, DR7, DQ2c], [HLA-B47, FC91,0, DR7, DQ2c] and [HLA-B57, SC61, DR7, DQ2d] carried the DQA1*0201 allele. All HLA-DR3, DQ2 and HLA-DR7, DQ2 extended haplotypes carried the DQB1*0201 allele. Every example of [HLA-B57, SC61, DR7, DQ9] carried the DQB1*0303 allele. Several associations between the DPB1 alleles and some HLA-DQ2- and DQ9-carrying extended haplotypes were identified. HLA-DPw2-encoding alleles, DPB1*0202 (50%, p < 0.001) and 0201 (30%), were found on the [HLA-B18, F1C30, DR3, DQ2b] extended haplotype. Every instance of the [HLA-B57, SC61, DR7, DQ9] extended haplotype carried the DPB1*0401 allele. Also, we have confirmed the associations of the DPB1*0101 and DPB1*0401 alleles with the [HLA-B8, SC01, DR3, DQ2a] extended haplotype. The analysis of homozygous typing cells carrying the [HLA-B44, FC31, DR7, DQ2c] extended haplotype showed that the DPB1*0401 and 0201 alleles were present at similar frequencies (37.5%), while the DPB1*1101 allele was found in only 25% of these haplotypes analyzed. Our results suggest that the constancy of the DNA of the HLA-B, DR, DQ regions may extend to the DP region and that the extent of such fixity varies, perhaps as the result of ethnic variability of the population studied.


Neural tube malformations: complex segregation analysis and recurrence risk.
A sample of 223 families with at least one child with anencephaly and/or spina bifida was ascertained in Southern Poland, where the incidence of neural tube malformations is 0.92/1,000. The recurrence risk in proband's sibs was 3.4%. The calculated heritability (h2) was 76%, implying a substantial contribution of genetic factors to the cause of neural tube defects. Complex segregation analysis was applied in an attempt to discriminate between the hypothesis of a single locus and that of quasi-continuity under multifactorial inheritance. The results excluded the hypothesis of dominant inheritance with full penetrance. The hypothesis of the two-allele model (at a single locus) fit the data with the same degree of exactness; however, for all hypotheses the estimated penetrance was low, and the phenocopy frequency was high. Less accurate conformity was observed for the multifactorial hypothesis. In view of very low penetrance and high frequency of phenocopies in single locus hypotheses and the finding that empirical data gave better support to the multifactorial model, the differences in chi 2 values should not be viewed as sufficient to discriminate between single locus and multifactorial models. The recurrence risks, assessed in the complex segregation analysis, showed an increase together with the growing number (r) of affected children. For constant r the recurrence risks decreased in successive pregnancies. Although discrimination between the mendelian and multifactorial inheritance models was incomplete, the risk values obtained can be employed in genetic counseling.


Biogeochemical effects of disturbance in shallow water sediment by macroalgae harvesting boats.
In the shallow water of Orbetello lagoon, macroalgae harvesting boats produce sediment disturbance. To evaluate the effect of this, during 2001-2002, a trial study was carried out in the lagoon in order to: verify seasonal and diurnal trends in nutrients and estimate the quantity of resuspended organic sediment. An unbalanced and balanced ANOVA (one and two way) analysis was applied. The disturbance did not produce strong and lasting eutrophication effects. In the seasonal survey, dissolved inorganic nitrogen (DIN) and soluble reactive phosphorus (SRP) showed significant decreases in disturbed areas at the end of the trial, while the control area showed a constant, significant increase. Dissolved organic nitrogen (DON) and phosphorus (DOP) significantly increased everywhere. In disturbed areas, sediment redox (Eh((NHE))) increased and porosity values decreased, contrary to the control area. Total organic carbon (TOC) remained unchanged in disturbed areas, but increased in the control area, where the C:P ration increased. The fall-out of sedimentary material resuspended by boat action for as far as 50 m from the boat route, was 189 g(dw)m(-2) made up mainly of organic matter. This disturbance could be the cause of change in vegetation in the lagoon.


[Erythropoietin enhances the therapy potency of autologous bone marrow stromal cells in a rat heart infarction model via phosphatidylinositol-3-kinase/Akt pathway].
Erythropoietin (EPO) induces angiogenesis and inhibits apoptosis through the phosphatidylinositol-3-kinase/Akt (PI3-K/Akt) pathway. Transplantation of mesenchymal stromal cells (MSC) has been shown to improve heart perfusion and function post myocardial ischemia. We investigated whether EPO enhances the therapeutic potency of MSC transplantation in rats with experimental myocardial infarction (MI). Wistar rats were divided into four groups (n=8 each): myocardial infarction (MI) group, EPO group, MSC group and MSC-EPO group. MI was made by ligating the anterior descending coronary artery. MSC was injected in the infarcted area immediately after ligation in MSC group and MSC-EPO group. EPO (3000 U/kg) was administered i.p. in EPO group and MSC-EPO group for 3 days post MI and on the 14th to 16th day post MI. Cardiac function was measured by echocardiography at 2 and 21 days after MI. MI size was measured, and the level of phosphorylated Akt was assessed by Western blot and immunohistology at 21 days post MI. LVEF was significantly lower at 21 days than that at 2 days in MI group while significantly increased in other 3 groups, especially in MSC-EPO group at 21 days than that at 2 days. MI size was significantly lower (20.7%+/-2.3% vs. 24.0%+/-2.3%, 26.0%+/-0.9%, 28.1%+/-1.5%, all P<0.05), capillary density was significantly higher (12.95+/-2.11 vs. 10.78+/-0.99, 10.43+/-1.52 and 6.31+/-0.69, all P<0.05) in MSC-EPO group at 21 days than that in other groups and the ratio of phosphorylated Akt to total Akt measured by Western blot was also significantly higher in MSC-EPO group than other groups (0.36 vs. 0.32, 0.31 and 0.28, all P<0.05). Compared to other groups, Bcl-2 was significantly up-regulated and Bax down-regulated in MSC-EPO group. Our results demonstrated that MSC transplantation and EPO infusion could improve cardiac function and EPO enhances the therapeutic potency of MSC transplantation via PI3-K/Akt pathways.


Alterations in follicular IGFBP mRNA expression and follicular fluid IGFBP concentrations during the first follicle wave in beef heifers.
The objective was to determine the pattern of IGFBP-2, -3 and -4 gene expression and follicular fluid concentrations of IGFBP-2, -3, -4 and -5 during emergence, selection and dominance of the first follicle wave of the estrous cycle in cattle and during exogenous steroid treatment. Heifers (n = 35) were ovariectomized at 36 (n = 7), 66 (n = 8), 84 (n = 12) and 108 (n = 8) h after the onset of estrus. Heifers in the 84 h ovariectomy group were sub-divided to receive either no treatment (n = 6) or were treated with a progesterone-releasing intravaginal device (n = 6, PRID) and 0.75 mg estradiol benzoate i.m. at the approximate time of ovulation, 30 h post estrus until ovariectomy. Within heifers the four largest follicles recovered following ovariectomy were ranked on size (F1, F2, F3 and F4). At 36 h IGFBP gene expression and follicular fluid IGFBP concentrations were similar in all follicles (F1-F4). Mean diameter of the F1 follicle increased (P < 0.05) between 36 and 84 h with no difference between 84 and 108 h. The F1 follicle had the highest (P < 0.05) concentration of estradiol compared with the F2, F3 and F4 at 84 and 108 h. There was no granulosa cell IGFBP-2 mRNA in F1 follicles at 84 or 108 h. Intrafolliclar IGFBP-2 concentrations were lower (P < 0.05) in the F1 compared with F3 and F4 follicles at 108 h. There was no difference in theca cell IGFBP-4 mRNA expression at 108h, but amounts of follicular fluid IGFBP-4 were lower (P < 0.05) in F1 follicles compared with F3 and F4 follicles at 108 h. IGFBP-3 mRNA was localized in the theca layer of all follicles examined with no difference in expression or follicular fluid concentrations during emergence, selection and dominance of the first follicle wave. IGFBP-5 concentrations were higher (P < 0.05) in follicular fluid of F3 follicles at 108 h compared with the F3 at 36 h. In conclusion follicular dominance was associated with low or decreased follicular fluid concentrations of IGFBP-4 and -5, increased estradiol and differential regulation of IGFBP production.


Interdisciplinary rehabilitation of a patient with Opitz C-syndrome and extensive craniofacial malformation.
A 24-year-old patient with C-syndrome and multiple congenital deformities was followed-up for his complete lifetime. The patient received extensive interdisciplinary rehabilitation of his complex somatic and craniofacial malformation. This article intends to show from the clinical point of view, how such patients can have profit from broad arrangements in specific periods of life, how far the rehabilitation can go in cases of good patients and parental compliance and how important an interdisciplinary cooperation is.


Digoxin-like substance(s) interfere(s) with serum estimations of the drug in cirrhotic patients.
We measured the levels of digoxin-like immunoreactivity in the serum of 40 volunteers (20 patients with liver cirrhosis and 20 healthy adults) before and after the administration of a 5-day standard regimen of digoxin. Serum digoxin levels (SDL) were evaluated with two different radioimmunoassay (RIA) kits--Amerlex Digoxin 125I RIA and Digoxin 125I RIA. Digoxin was detectable by each RIA kit in 10 and 15% of controls and 50 and 60% of cirrhotic patients before the administration of the drug, respectively. At the end of the treatment with digoxin, SDL were significantly higher in cirrhotics when compared with those of controls. This study provides evidence that digoxin-like substance(s) is (are) implicated in the detection of high SDL in patients with histologically confirmed liver cirrhosis.


MRI manifestations of liver epithelioid and nonepithelioid angiomyolipoma.
To retrospectively analyze the magnetic resonance imaging (MRI) manifestations of liver AML and compare the MRI manifestations of epithelioid and nonepithelioid angiomyolipoma (AML). The study comprised a retrospective analysis of 11 patients whose hepatic AML was confirmed by surgical pathology. Routine MRI examination was performed in 11 patients, of which five were cases of epithelioid AML and six were cases of nonepithelioid AML. One case of nonepithelioid AML underwent a plain MRI scan only, while the remaining 10 patients underwent MRI and dynamic contrast-enhanced scans. Chemical shift imaging detected more fat component cases than frequency the saturation method did (7/11 vs. 3/11). The difference was not statistically significant, however (P = 0.236). The degree of fatty component was different between epithelioid and nonepithelioid AML, but there was no significant difference between them (P = 0.766). Of the 10 cases in which enhancement scans were performed, nine had hyperenhancement in the arterial phase, and nine had capsule enhancement on delayed phase. The amount of fat content is not related to whether the tumor is epithelioid or nonepithelioid. Under dynamic contrast-enhancement MRI, epithelioid AML shows enhancement patterns similar to those of classic AML rich in vascular smooth muscles.


Electrostatics for probing lone pairs and their interactions.
The value of the molecular electrostatic potential minimum (Vmin ) and its topographical features (position, as well as the eigenvalues and eigenvectors of the corresponding Hessian matrix) are recently proposed as the criteria for characterizing a lone pair (Kumar A. et al., J. Phys. Chem. 2014, A118, 526). This electrostatic characterization of lone pairs is examined for a large number of small molecules employing MP4/6-311++G(d,p)//MP2/6-311++G(d,p) theory. The eigenvector of the Hessian matrix corresponding to its largest eigenvalue (λmax ), is found to be directed toward the lone pair-bearing-atom, with λmax showing a strong linear correlation with Vmin . Large magnitudes of Vmin and λmax indicate a charge-dense lone pair. The topographical features of Vmin are seen to provide insights into the interactive behavior of the molecules with model electrophiles, viz. HF, CO2 , and Li+ . In all the complexes of HF and majority of the other complexes, the interaction energy (Eint ) correlates well with the respective Vmin, value, but for some deviations occurring due to other competing secondary interactions. The electrostatic interactions are found to be highly directional in nature as the orientation of interacting atom correlates strongly to the position of lone pair. In summary, the present study on a large number of test molecules shows that electrostatics is able to probe lone pairs in molecules and offers a simple interpretation of chemical reactivity. © 2017 Wiley Periodicals, Inc.


Comparison of the immunosuppressive effects of cyclosporine, lipid-soluble anesthetics, and calmodulin antagonists. Response to exogenous interleukin 2.
The purpose of these investigations was to compare the immunosuppressive mechanism of cyclosporine (CsA) with those of lipid-soluble local anesthetics and calmodulin antagonists. Chlorpromazine (CPZ) and pentobarbital (PB) both inhibit lymphocyte activation by attenuating sodium and potassium ion potentials. CPZ and N-(6-aminohexyl)-5-chloro-1-naphthalene sulfonamide (W-7) can also block calcium-dependent activation processes by inhibition of calmodulin and protein kinase C. All four compounds were found to suppress human and murine lymphoproliferation to both alloantigen or mitogen in a dose-dependent and saturable manner. Exogenous interleukin-2 (IL-2) restored mitogenic responsiveness to cultures suppressed using W-7 and CsA, but not to lymphocytes suppressed with either CPZ or PB. Cytofluorographic analysis revealed that the degree of suppression in drug-treated lymphocytes was significantly correlated with the surface expression of receptors for transferrin and interleukin-2. Inhibition of IL-2 activation by PB was demonstrated to result from a blockade of the mitogenic growth factor signal using the IL-2-dependent cell line HT-2. Thus, the mechanism of action of cyclosporine can be differentiated from those of anesthetic immunosuppressants at the level of responsiveness to interleukin-2. The data support the hypothesis that cyclosporine may be an antagonist of calmodulin that selectively blocks early events in T lymphocyte activation leading to IL-2 synthesis, but does not inhibit the expression or function of the IL-2 receptor.


Regression of left ventricular hypertrophy in children following the Ross procedure.
Left ventricular hypertrophy (LVH) frequently accompanies the progression of aortic valve disease in children. The extent of LVH regression following surgical relief of aortic valve disease in children has not been clearly elucidated. We hypothesized that significant regression of LVH will occur in children following the Ross procedure. We examined LVH over time in children <18 years of age who underwent the Ross procedure. Left ventricular mass index (LVMI) and corresponding z scores were calculated based on height, age and gender. Left ventricular hypertrophy was defined as an LVMI of > 39 g/m(2.7) and a z score of >1.6. Twenty-five children underwent the Ross procedure. The left ventricular mass increased proportionally with the growth of the child from baseline to the latest follow-up at 7.3 ± 2.9 years (121.1 ± 81.5 vs 133.1 ± 79.8 g, P = 0.4). However, 96% (24/25) of children demonstrated LVMI regression from baseline. Mean LVMI decreased from 70.8 ± 31.2 to 41.8 ± 16.6 g/m(2.7) (P < 0.001). Similarly, LVMI z scores decreased from 2.2 ± 1.2 to 0.2 ± 1.9 (P < 0.001). Freedom from LVH was 83% at 10 years. Examination of LVMI and z scores over time demonstrated that the largest decrease occurred after the first year, with continued gradual decline over 10 years of follow-up. The Ross procedure is effective in reversing LVH in children with aortic valve disease.


Stability of midazolam hydrochloride in extemporaneously prepared flavored gelatin.
The stability of midazolam hydrochloride in flavored gelatin was evaluated after storage at 4 degrees C for 14 days and at -20 degrees C for 28 days. A flavored liquid gelatin mixture was prepared and mixed with midazolam hydrochloride injection in final concentrations of midazolam 1 and 2 mg/mL. Gelatin cups containing 5 and 15 mg of midazolam were prepared by measuring appropriate volumes of the gelatin stock solutions and were stored in a refrigerator at 4 degrees C or in a freezer at -20 degrees C. Immediately after preparation and at 7 and 14 days, three refrigerated and three frozen gelatin samples of each midazolam concentration were visually inspected, tested for pH, and assayed for midazolam concentration by high-performance liquid chromatography. The frozen gelatin samples were also evaluated at 21 and 28 days; three whole and three partial gelatin samples were assayed for midazolam content to determine the uniformity of drug distribution within each sample. All samples maintained greater than 96% of the initial midazolam concentration throughout the study. There was no appreciable change in color, odor, or pH. The midazolam content of the gelatin in the cups was uniform. An extemporaneously compounded preparation of midazolam hydrochloride in flavored gelatin was stable when stored for 14 days at 4 degrees C and for 28 days at -20 degrees C. Distribution of midazolam hydrochloride in the gelatin was uniform.


The quality of assessment visits in community nursing.
The aim of this study was the measurement of the quality of assessment visits of community nurses in The Netherlands. Process criteria were derived for the quality of the assessment visits from the quality standards of community nursing care established by Appelman et al. Over a period of 8 weeks, a representative sample of 108 community nurses and 49 community nursing auxiliaries at 47 different locations paid a total number of 433 assessment visits. The nursing activities were recorded for each visit. The results suggested that most assessment visits (88%) were paid by community nurses. During the assessment visits, community nurses more often paid attention to questions and expectations of the patient than nursing auxiliaries did. Furthermore, the quality of taking case histories in the actual practice of assessment appeared to be high in general. However, nearly half of the nurses did not enquire whether the patient received care from other health care professionals. The drafting of the care plan was, on average, of a lesser quality. In particular, the re-assessment of patients was not systematically planned.


A role for threonine 302 in the mechanism-based inactivation of P450 2B4 by 2-ethynylnaphthalene.
2-Ethynylnaphthalene (2EN) is a mechanism-based inactivator of P450 2B4 that covalently modifies an amino acid in the peptide Glu273-Met314 with a 2-naphthylacetyl group [Roberts et al. (1994) Biochemistry 33, 3766-3771]. Truncated 2B4 lacking amino acids 2-27, 2B4 (Delta2-27), was expressed in Escherichia coli, purified, and found to catalyze the oxidation of 2EN to 2-naphthylacetic acid (2NA). The metabolism of 2EN resulted in the inactivation and covalent modification of the protein moiety as we have previously reported with P450 2B4 purified from the livers of phenobarbital-induced rabbits. The rate constants of inactivation of the O-deethylation activity of 7-ethoxy-4-trifluoromethylcoumarin (EFC) were 0.15 +/- 0.01 and 0.20 +/- 0.05 min-1 for the protein purified from rabbit liver and 2B4 (Delta2-27), respectively. A protein in which threonine 302 was replaced with alanine, P450 2B4 (Delta2-27, T302A), was inactivated by 2EN with a much slower rate constant (0.05 +/- 0.01 min-1) and formed 1.8-fold more 2NA as compared to P450 2B4 (Delta2-27) over a 10-min incubation. When the formation of 2NA was supported by cumene hydroperoxide, 2B4 (Delta2-27, T302A) formed 30% less product than 2B4 (Delta2-27) over a 5-min incubation. After incubation with [3H]2EN and NADPH, P450 2B4 (Delta2-27) had significant radioactivity associated with the P450 in an NADPH-dependent manner when the incubation mixture was analyzed by SDS-PAGE followed by autoradiography and 10-fold more radioactivity associated with the P450 as compared to P450 2B4 (Delta2-27, T302A) when analyzed by reverse-phase HPLC. Thus, threonine 302 is not required by 2B4 for oxidation of 2EN or EFC but appears to play an important role in the inactivation of P450 2B4 by 2EN and the covalent labeling of the P450 protein by 2EN.


Aberrant signaling in the TNFalpha/TNF receptor 1 pathway of the NZM2410 lupus-prone mouse.
The purpose of this study was to evaluate the ability to induce TNFalpha-dependent apoptosis in vivo in predisease lupus-prone NZM2410 and derived B6.NZM congenic mouse strains. An endotoxicosis model that utilizes LPS and d-galactosamine to induce mortality by TNFalpha/TNFR1-dependent hepatocyte apoptosis was used to assess TNFalpha production, apoptotic signaling, and effects on the production of IL-6 and IL-10. NZM2410 was found to be resistant to endotoxicosis and to produce significantly less TNFalpha-induced IL-6 and IL-10. At low doses of LPS, partial resistance was associated with the Tnfa(w) allele. At higher doses of LPS, partial resistance cosegregated with lupus-susceptibility loci and functionally mapped downstream of caspase 3. Additional partial resistance in NZM2410 was also found upstream of FADD. These results demonstrate the existence of multiple defects in the TNFalpha/TNFR1 signaling pathway in the NZM2410 mouse and their relevance to lupus pathogenesis is discussed.


Comparative studies on alveolar macrophages and polymorphonuclear leukocytes. III. Difference spectra of their cellular and subcellular fractions.
The respiratory pigments of rabbit polymorphonuclear leukocytes (PMN) and alveolar macrophages (A-MO) were compared in a spectrophotometric study conducted at liquid nitrogen temperature. In the difference spectra of the KCN-treated minus the untreated states and of the reduced minus the oxidized states, the cellular and granular fractions of PMN showed sharp absorption maxima identical with the absorption bands of myeloperoxidase (MPO). Even though A-MO revealed some guaiacol-peroxidation activity, the difference spectra of cellular and subcellular A-MO fractions did not show an MPO spectrum. The enzyme catalyzing the guaiacol peroxidation by A-MO appears to be an enzyme other than the MPO found in PMN. Despite the absence of the MPO spectrum, the difference spectra of A-MO granules when measured with KCN, dithionite, and succinate showed characteristic absorption bands of mitochondrial cytochromes, in contrast to the difference spectra of PMN, which showed far smaller cytochrome absorption bands. The results obtained suggest that the phagocytic metabolism of rabbit A-MO depends on mitochondrial respiration for its energy supply.


The role of glutamate and its receptors in the proliferation, migration, differentiation and survival of neural progenitor cells.
The mammalian central nervous system derives from multipotent neural progenitor cells (NPCs) of the developing brain. During development the progenitor cells have enormous potential. They proliferate actively and differentiate into all the three main cell types, i.e., neurons, astrocytes and oligodendrocytes, of the adult brain through a tightly regulated process that coordinates cell proliferation, survival, migration, differentiation and apoptosis. This process is regulated by multiple extracellular signals including neurotrophic factors, chemoattractants and neurotransmitters in a coordinated manner. The main excitatory neurotransmitter glutamate is involved in promoting and/or inhibiting the proliferation, survival, migration and differentiation of NPCs acting via ionotropic or metabotropic receptors. The role of glutamate in the regulation of cortical NPCs has been most extensively studied. Glutamate appears to have a similar role in hippocampal, striatal as well as adult neural progenitors. Ionotropic α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA)/kainate (KA) receptors and metabotropic glutamate receptor 5 (mGluR5) are expressed early during embryonic development as well as in the neurogenic zones of the adult brain. Ca(2+)-permeable AMPA/KA receptors are initially of importance for cell proliferation and neuronal motility. At later stages of development N-methyl-D-aspartate (NMDA) receptors have a more prominent role. MGluR5, which is the main metabotropic glutamate receptor during early development, is expressed in early progenitors and radial glial cells. Activation of this receptor promotes the proliferation and survival of NPCs. MGluR5 is involved in the extension of radial glial processes and in regulation of the migration of early cortical neurons.


Over-expression of OsPIN2 leads to increased tiller numbers, angle and shorter plant height through suppression of OsLAZY1.
Crop architecture parameters such as tiller number, angle and plant height are important agronomic traits that have been considered for breeding programmes. Auxin distribution within the plant has long been recognized to alter architecture. The rice (Oryza sativa L.) genome contains 12 putative PIN genes encoding auxin efflux transporters, including four PIN1 and one PIN2 genes. Here, we report that over-expression of OsPIN2 through a transgenic approach in rice (Japonica cv. Nipponbare) led to a shorter plant height, more tillers and a larger tiller angle when compared with wild type (WT). The expression patterns of the auxin reporter DR5::GUS and quantification of auxin distribution showed that OsPIN2 over-expression increased auxin transport from the shoot to the root-shoot junction, resulting in a non-tissue-specific accumulation of more free auxin at the root-shoot junction relative to WT. Over-expression of OsPIN2 enhanced auxin transport from shoots to roots, but did not alter the polar auxin pattern in the roots. Transgenic plants were less sensitive to N-1-naphthylphthalamic acid, an auxin transport inhibitor, than WT in their root growth. OsPIN2-over-expressing plants had suppressed the expression of a gravitropism-related gene OsLazy1 in the shoots, but unaltered expression of OsPIN1b and OsTAC1, which were reported as tiller angle controllers in rice. The data suggest that OsPIN2 has a distinct auxin-dependent regulation pathway together with OsPIN1b and OsTAC1 controlling rice shoot architecture. Altering OsPIN2 expression by genetic transformation can be directly used for modifying rice architecture.


Micelles of imidazolium-functionalized polystyrene diblock copolymers investigated with neutron and light scattering.
We synthesize a series of block copolymers comprising a polystyrene (PS) block and an imidazolium-functionalized PS (IL) block and characterize their assembly properties. We use small-angle neutron scattering and dynamic light scattering to determine the micelle size and shape in dilute solutions and to assess the micelle interactions in concentrated solutions. By studying a series of copolymers with fixed PS block length, we find that the length of the IL block governs the micelle dimensions. Our data suggest that these copolymers form elongated micelle structures where the IL block is extended in the micelle core. We find that these micelles can sequester water and that interactions between the micelles lead to structure factor peaks at elevated concentrations.