Genetic characterization of a novel calicivirus from a chicken.
We describe the identification and genetic characterization of a novel enteric calicivirus, detected by transmission electron microscopy and RT-PCR in two clinically normal chickens and in a chicken with runting and stunting syndrome from different flocks in southern Germany. Positive findings were confirmed by sequencing. The complete nucleotide sequence and genome organization of one strain (Bavaria/04V0021) was determined. The genome of the Bavaria virus is 7,908 nt long and contains two coding open reading frames. Phylogenetic analysis of the deduced partial 2C helicase/NTPase, 3C cysteine protease, RNA-dependent RNA polymerase and complete VP1 capsid protein amino acid sequences showed that the virus is genetically related to but distinct from sapoviruses and lagoviruses. Morphologically, the Bavaria virus particles are 37-42 nm in diameter and exhibit characteristic cup-shaped surface depressions.


Synthesis and evaluation of mucoadhesive acryloyl-quaternized PDMAEMA nanogels for ocular drug delivery.
Poly((2-dimethylamino)ethyl methacrylate) (PDMAEMA) nanogels were synthesized via surfactant-free free-radical polymerization technique in aqueous conditions utilizing N,N'-methylene-bis-acrylamide (MBA) as a crosslinking agent. The PDMAEMA nanogels were subsequently quaternized with acryloyl chloride in order to yield mucoadhesive materials which incorporate two mucoadhesive concepts; electrostatic interactions and covalent bond forming acrylate groups. The native PDMAEMA nanogels were found to exhibit good mucoadhesive properties on ex vivo bovine conjunctival tissues, which was found to increase proportionally with the degree of quaternization. With a view to determine the ocular drug delivery capabilities of the materials, both quaternized and native nanogels were loaded with pilocarpine hydrochloride via an absorption method, and their in vitro release profiles were analysed. The nanogels were found to exhibit a high loading capacity (>20% of total weight) and a sustained release over 6h.


Effects of conventional argon panretinal laser photocoagulation on retinal nerve fibre layer and driving visual fields in diabetic retinopathy.
To determine the effects of argon green panretinal laser photocoagulation on retinal nerve fibre layer thickness, threshold visual fields, and Estermann full-binocular visual fields over time in diabetic retinopathy. Prospective, pilot clinical study. Time-domain optical coherence tomography (TD-OCT) of the optic nerve head and 24-2 SITA-Fast Humphrey/Estermann visual fields (HVF, EVFs) recorded at baseline, 10 weeks, and 6 months post laser. Quantitative field analysis of central 10 degrees, 24 degrees, and binocular visual fields. A total of 10 eye samples were subjected to uncomplicated multiple-session 100 ms panretinal laser using 2000 burns, 300-microm spot, and mean power of 136 mW (SD+/-39.3). TD-OCT detected and quantified an increase in mean retinal nerve fibre layer thickness at 10 weeks (+8 microm; P<0.05) and progressive thinning at 6 months (-4 microm; P<0.05) compared with baseline. Mean threshold sensitivities, and 10 degrees and 24 degrees HVF improved at both time points in the majority (9 of 10 and 8 of 10) of patients. EVFs showed no significant change with treatment. This pilot study shows that conventional argon laser panretinal photocoagulation may increase the retinal nerve fibre layer thickness in the short term, presumably related to laser-induced axonal injury, with progressive thinning of nerve fibre layer over the long term. The 10 degrees and 24 degrees visual fields improved significantly after laser with no adverse effects on the UK standard driving fields.


[Evaluation of 2 school mediator courses on alcohol and tobacco problems. Collective analysis versus group analysis].
Secondary school pupils were trained to serve as mediators on alcohol and tobacco problems in their classes. Evaluation was based on danger in behaviour regarding tobacco and alcohol in their classmates. Classes without any influence of mediators served as controls. Increased knowledge and motivation to abstain from alcohol and tobacco were measured. In this survey the individual dynamics of each class and the teacher's influence interfered with the mediators effect. If these facts are taken into account, such projects may become useful tools in health education.


Molecular characterization and genetic mapping of class I and class II MHC genes of the domestic cat.
The major histocompatibility complex (MHC) of the domestic cat has been poorly characterized to date, primarily because of numerous difficulties in the preparation of allotypic sera. We present here a comparative analysis of class I and class II genes in domestic cat populations using molecular probes of the MHC from man and mouse. The cat possesses a minimum of 20 class I loci and 5 class II genes per haploid genome. Class I genes of the domestic cat expressed limited restriction fragment length polymorphism. The average percent difference of the size of DNA fragments between individual cats was 9.0%, a value five times lower than the value for mice, but comparable to the human DNA polymorphism level. Class I and class II genes were both genetically mapped to feline chromosome B2 using a panel of rodent x cat somatic cell hybrids. Since feline chromosome B2 is syntenically homologous to human chromosome 6 and mouse chromosome 17, these results affirm the linkage conservation of the MHC-containing linkage group in the three mammalian orders.


On the structural differences between markers and genomic AC microsatellites.
AC microsatellites have proved particularly useful as genetic markers. For some purposes, such as in population biology, the inferences drawn depend on the quantitative values of their mutation rates. This, together with intrinsic biological interest, has led to widespread study of microsatellite mutational mechanisms. Now, however, inconsistencies are appearing in the results of marker-based versus non-marker-based studies of mutational mechanisms. The reasons for this have not been investigated, but one possibility, pursued here, is that the differences result from structural differences between markers and genomic microsatellites. Here we report a comparison between the CEPH AC marker microsatellites and the global population of AC microsatellites in the human genome. AC marker microsatellites are longer than the global average. Controlling for length, marker microsatellites contain on average fewer interruptions, and have longer segments, than their genomic counterparts. Related to this, marker microsatellites show a greater tendency to concentrate the majority of their repeats into one segment. These differences plausibly result from scientists selecting markers for their high polymorphism. In addition to the structural differences, there are differences in the base composition of flanking sequences, marker flanking regions being richer in C and G and poorer in A and T. Our results indicate that there are profound differences between marker and genomic microsatellites that almost certainly affect their mutation rates. There is a need for a unified model of mutational mechanisms that accounts for both marker-derived and genomic observations. A suggestion is made as to how this might be done.


Additive effect of diabetes and systemic hypertension on the immune mechanisms of atherosclerosis.
In order to evaluate the changes in humoral immunity due to one and two atherogenic factors (systemic hypertension and/or diabetes mellitus), we investigated 350 women divided into four groups: (1) 65 insulin-dependent (type I) non-hypertensive diabetics; (2) 92 systemic hypertensive non-diabetic subjects; (3) 64 hypertensive insulin-dependent diabetics; and (4) 129 non-hypertensive and non-diabetic women as a control group. All subjects had no coronary artery disease. The humoral immunity was evaluated by (1) circulating immune complexes, (2) total serum complement, (3) C3 fraction of complement, and (4) circulating antitissue antibodies (antivascular and antisclerotic-vascular). The patients with atherosclerotic risk factors (diabetes and/or hypertension) had significantly (P < 0.001) elevated levels of total complement, C3 fraction and circulating complexes compared with the control group. Total complement and circulating complexes levels were most elevated in patients with a combination of diabetes and hypertension. Similarly, these patients had the highest frequency of antitissue antibodies. In summary, the parameters of humural immunity were more changed in patients with two risk factors (diabetes and hypertension) compared to patients with only one risk factor. It is possible that these immunological changes appeared earlier than clinical symptoms of atherosclerosis and they could be used as an early prognostic test for predisposition to atherosclerotic vascular complications.


Conformational Plasticity of the Immunoglobulin Fc Domain in Solution.
Fragment crystallizable (Fc) region of immunoglobulin G (IgG) antibody binds to specific Fc receptors (FcγRs) to control antibody effector functions. Currently, engineered specific Fc-FcγR interactions are validated with a static conformation derived from the crystal structure. However, computational evidence suggests that the conformational variability of Fcs plays an important role in receptor recognition. Here we elucidate Fc flexibility of IgG1, IgG2, and IgG1 Fc with mutations (M255Y/S257T/T259E) in solution by small-angle X-ray scattering (SAXS). Measured SAXS profiles and experimental parameters show variations in flexibility between Fc isotypes. We develop and apply a modeling tool for an accurate conformational sampling of Fcs followed by SAXS fitting. Revealed conformational variability of the CH2 domain as low as 10 Å in displacement, illustrates the power of the atomistic modeling combined with SAXS. This inexpensive SAXS-based approach offers to improve the engineering of antibodies for tailoring Fc receptor interactions through altering and measuring Fc flexibility.


Tissue levels of leu-enkephalin in rats with adjuvant arthritis.
To study the level of leu-enkephalin in bone and joint tissues and in the spinal cord of rats with adjuvant arthritis, arthritis was induced in Lewis rats by the injection of Mycobacterium butyricum in Freund's incomplete adjuvant (FIA). Immunoelectron microscopy (IEM) was used to monitor the cellular distribution of leu-enkephalin in control and arthritis groups, and radioimmunoassay (RIA) was used to measure the concentration in the tissues. The results of IEM showed increased levels of leu-enkephalin in the matrix of the sciatic nerve, in nerve fibres in the synovial membrane and periosteum, as well as in fibroblasts and endothelial cells of the periosteum in arthritic groups. In macrophage-like cells of the synovial membrane as well as monocyte and polymorphonuclear lineage cells in the bone marrow, the level of leu-enkephalin was decreased in the arthritic group. The results of RIA showed that the concentration of leu-enkephalin was lower in the ankle and increased in the spinal cord of arthritic animals compared with controls. In conclusion, leu-enkephalin levels were decreased in joints and in bone marrow, but increased in nerve tissues in the group with arthritis. Further studies are needed to show whether leu-enkephalin is involved in a process that serves to limit the effect of immunisation.


Neural correlates to automatic behavior estimations from RGB-D video in epilepsy unit.
To augment neural monitoring, a minimally intrusive multi-modal capture system was designed and implemented in the epilepsy clinic. This system provides RGB-D audio-video synchronized with patient electrocorticography (ECoG), which records neural activity across cortex. We propose an automated approach to studying the human brain in a naturalistic setting. We demonstrate coarse functional mapping of ECoG electrodes correlated to contralateral arm movements. Motor electrode mapping was generated by analyzing continuous movement data recorded over several hours from epilepsy patients in hospital rooms. From these recordings we estimate the kinematics of patient hand movement behaviors using computer vision algorithms. We compare movement behaviors to neural data collected from ECoG, specifically high-γ (70-110 Hz) spectral features. We present a functional map of electrode responses to natural arm movements, generated using a statistical test. We demonstrate that our approach has the potential to aid in the development of automated functional brain mapping using continuous video and neural recordings of patients in clinical settings.


Medication reconciliation: developing and implementing a program.
During the past 5 years since the medication reconciliation process was formalized and automated, it has become an independent redundancy. The patient intervention rates are maintained at 30% to 35%, with ADE rates related to medication reconciliation at zero. The medication process takes into account the accuracy and appropriateness of restarting prehospital medications and current ICU medications. It includes the omission of important home medications along with inaccuracies of dosages and frequencies. This form assures that the patient is receiving continuity of care ad decreases complications of the patients health related to the changing of medications. Until recently this concept was disseminated by the staff without consistent administrative support. It was a process developed by nurses and perpetuated by nurses. Recently the administration has mandated that the process be implemented throughout the institution. A Hopkins health care-based collaborative is working to implement medication reconciliation hospital wide. The challenge exists in standardizing a process that is now specific to each functional unit. Multidisciplinary monthly meetings provided a forum for working through the barriers to incorporate these changes. This low-cost, high-impact safely initiative, if planned and performed strategically, can have a significant effect on patient safety.


Is endoscopic ultrasound needed as an add-on test for gallstone diseases without choledocholithiasis on multidetector computed tomography?
Choledocholithiasis commonly occurs in patients with symptomatic cholelithiasis. Although the recently developed multidetector computed tomography (MDCT) scan enhances the ability to diagnose choledocholithiasis, this technique is considered to have some limitations for evaluating the common bile duct (CBD). The purpose of this study was to evaluate the necessity for performing endoscopic ultrasound (EUS) as an add-on test to detect choledocholithiasis in patients who were diagnosed with gallstone disease without choledocholithiasis based on MDCT. Three hundred twenty patients with gallstone disease and no evidence of CBD stones according to MDCT underwent EUS between March 2006 and April 2011. If CBD stones were suspected based on the EUS results or clinical symptoms, a final diagnosis was obtained by endoscopic retrograde cholangiopancreatography (ERCP). The patients' medical records were retrospectively analyzed based on clinical symptoms, biochemical findings, and results of the imaging studies. CBD stones were not detected with MDCT in 41 (12.8 %) out of 320 patients with gallstone disease. The causes for these discrepancies could be attributed to small stone size (n = 19, 46.3 %), isodensity (n = 18, 43.9 %), impacted stones (n = 1, 2.4 %), and misdiagnosis (n = 3, 7.3 %). If EUS were used as a triage tool, unnecessary diagnostic ERCP and its complications could be avoided for 245 (76.6 %) patients. MDCT may not be a primary technique for detecting CBD stones. EUS should be performed instead as an add-on test to evaluate the CBD for patients with gallstone-related disease. In particular, EUS should be routinely recommended for patients with abnormal liver enzyme levels, pancreatitis, and dilated CBD.


Further Tests of a Dynamic-Adjustment Account of Saccade Targeting During the Reading of Chinese.
There are two accounts of how readers of unspaced writing systems (e.g., Chinese) know where to move their eyes: (a) saccades are directed toward default targets (e.g., centers of words that have been segmented in the parafovea); or (b) saccade lengths are adjusted dynamically, as a function of ongoing parafoveal processing. This article reports an eye-movement experiment supporting the latter hypothesis by demonstrating that the slope of the relationship between the saccade launch site on word N and the subsequent fixation landing site on word N + 1 is > 1, suggesting that saccades are lengthened from launch sites that afford more parafoveal processing. This conclusion is then evaluated and confirmed via simulations using implementations of both hypotheses (Liu, Reichle, & Li, 2016), with a discussion of these results for our understanding of saccadic targeting during reading and existing models of eye-movement control.


Stressed out? Healing Tips for Newly Reprogrammed Neurons.
How do astrocyte-derived neurons deal with the sudden loss of their glial identity? Exciting new findings from Gascón et al. (2016) single out metabolic conversion as a critical checkpoint for direct neuronal reprogramming.


Regulation of renin secretion by renal juxtaglomerular cells.
A major rate-limiting step in the renin-angiotensin-aldosterone system is the release of active renin from endocrine cells (juxtaglomerular (JG) cells) in the media layer of the afferent glomerular arterioles. The number and distribution of JG cells vary with age and the physiological level of stimulation; fetal life and chronic stimulation by extracellular volume contraction is associated with recruitment of renin-producing cells. Upon stimulation of renin release, labeled renin granules "disappear;" the number of granules decrease; cell membrane surface area increases in single cells, and release is quantal. Together, this indicates exocytosis as the predominant mode of release. JG cells release few percent of total renin content by physiological stimulation, and recruitment of renin cells is preferred to recruitment of granules during prolonged stimulation. Several endocrine and paracrine agonists, neurotransmitters, and cell swelling converge on the stimulatory cyclic AMP (cAMP) pathway. Renin secretion is attenuated in mice deficient in beta-adrenoceptors, prostaglandin E(2)-EP4 receptors, Gsα protein, and adenylyl cyclases 5 and 6. Phosphodiesterases (PDE) 3 and 4 degrade cAMP in JG cells, and PDE3 is inhibited by cyclic GMP (cGMP) and couples the cGMP pathway to the cAMP pathway. Cyclic AMP enhances K(+)-current in JG cells and is permissive for secretion by stabilizing membrane potential far from threshold that activates L-type voltage-gated calcium channels. Intracellular calcium paradoxically inhibits renin secretion likely through attenuated formation and enhanced degradation of cAMP; by activation of chloride currents and interaction with calcineurin. Connexin 40 is necessary for localization of JG cells in the vascular wall and for pressure- and macula densa-dependent suppression of renin release.


Atypical pattern of discriminating sound features in adults with Asperger syndrome as reflected by the mismatch negativity.
Asperger syndrome, which belongs to the autistic spectrum of disorders, is characterized by deficits of social interaction and abnormal perception, like hypo- or hypersensitivity in reacting to sounds and discriminating certain sound features. We determined auditory feature discrimination in adults with Asperger syndrome with the mismatch negativity (MMN), a neural response which is an index of cortical change detection. We recorded MMN for five different sound features (duration, frequency, intensity, location, and gap). Our results suggest hypersensitive auditory change detection in Asperger syndrome, as reflected in the enhanced MMN for deviant sounds with a gap or shorter duration, and speeded MMN elicitation for frequency changes.


Superior oblique muscle surgery.
The anatomy and actions of the superior oblique muscle are discussed as a basis for logical surgical procedures. Weakening procedures are indicated for overaction or for a short superior oblique tendon. Tenectomy is performed nasal to the superior rectus while selective tenotomies for bilateral overaction are performed temporal to the superior rectus. Recession of the whole tendon on an adjustable suture is preferred for unilateral superior oblique overaction. Tendon tucking for unilateral superior oblique palsy is performed temporal to the superior rectus and inevitably causes a degree of pseudo-Brown's syndrome. Tucks may be used bilaterally in bilateral cases. Alternatively, anterior tendon advancement corrects tensional symptoms. It may be graded from a maximum advancement to the upper border of the lateral rectus to suit the degree of tension. Adjustable sutures may be used. Superior oblique tendon transfer for long-standing third nerve palsies may produce paradoxical eye movements in the long-term due to scarring.


Gefitinib-sensitive mutations of the epidermal growth factor receptor tyrosine kinase domain in chinese patients with non-small cell lung cancer.
Studies have shown that mutations in the epidermal growth factor receptor (EGFR) tyrosine kinase domain are associated with response of lung cancer to gefitinib (Iressa, AstraZeneca Corp., Shanghai, China). A higher incidence of EGFR mutation was observed in non-small cell lung cancer (NSCLC) patients of Japanese origin compared with those of American origin. However, no data about such mutations in Chinese patients with NSCLC could be obtained. Primary NSCLC tissues were obtained for analysis of mutations in exons 18 to 21 of EGFR from a total of 76 patients, of whom 54 did not receive gefitinib therapy and 22 did. PCR products were sequenced directly and mutations were confirmed by an independent PCR and sequence analysis. All types of mutation were cloned and sequenced. A total of 10 types of mutation were found in the series of patients, including two different silent mutations in exon 20 from 11 patients. More than half of the silent mutations (6 of 11) in exon 20 coexisted with other mutations. Mutations were more frequent in adenocarcinoma (17 of 35; 48.6%) compared with squamous carcinoma (1 of 19; 5.3%) among untreated patients. Similar mutations were observed in all seven gefitinib-treated patients with partial response, and no mutations were detected in all eight patients with progressive disease (P < 0.001), except two silent mutations. Three mutations were observed in seven patients with stable disease. Mutations in the epidermal growth factor receptor tyrosine kinase domain in lung adenocarcinomas from Chinese patients were more frequent than reported previously in lung adenocarcinomas from American patients. Such mutations were well correlated with tumor response to gefitinib.


Effects of alpha,beta-methylene ATP on potentiation of contractions to field stimulation of rat vas deferens by carbachol.
Carbachol (0.1-300 mumol/L) potentiated contractions to field stimulation (0.1 Hz, 1 ms, supramaximal V) in the rat epididymal and prostatic vas deferens. Desensitization of P2-purinoceptors by exposure to alpha,beta-methylene ATP (30 mumol/L) markedly reduced (greater than 80%) the potentiating effect of carbachol in the prostatic vas deferens but only moderately reduced (about 20%) the maximal stimulated response to carbachol in the epididymal segment. The presence of prazosin (10 mumol/L) and yohimbine (10 mumol/L), being selective alpha 1- and alpha 2-adrenoceptor antagonists, did not modify the attenuation of carbachol potentiation caused by alpha,beta-methylene ATP treatment. At 0.1 mmol/L, alpha,beta-methylene ATP had no significant effect on the binding of [3H]QNB to muscarinic cholinergic receptors. It is concluded that carbachol may potentiate the contractions to field stimulation in the prostatic vas deferens via an enhancement of purinergic neurotransmission. The molecular mechanism of carbachol potentiation in the epididymal vas deferens remains to be established.


[Fibrosing alveolitis following Legionella pneumonia].
We reported a case of fibrosing alveolitis following Legionella pneumonia. A 62-year-old man was admitted to our hospital with fever after a visit to a hot spring. Chest X-ray films on admission demonstrated air-space consolidation in the right lower lung. Legionella pneumonia was diagnosed because the patient had elevated serum antibody to Legionella pneumophila serogroup Ia and tested positive for urinary antigen. Although he was initially treated with rifampicin and erythromycin, he experienced drug-induced eruptions. Antibiotic therapy was accordingly changed to clarithromycin, levofloxacin, and minocycline, which together alleviated the patient's clinical symptoms but delayed radiologic regression. Chest X-ray films 2 months after the onset of illness revealed diffuse ground-glass opacities and progressive reduction of volume in the right lung. Long-term corticosteroid treatment was required. Three and half months after disease onset, fever recurred with the appearance of interstitial shadows in the left lung and positive tests for urinary antigen. Increasing the corticosteroid dose resolved the patient's symptoms.


Quantification of synapse turnover in cell culture.
The on and off rates of synaptogenesis can be quantitated using a cell culture system in which embryonic retinal cells form functional synapses with striated muscle cells. Quantification showed that synapse formation and termination can occur simultaneously in culture. Quantification also revealed that some retina-muscle synapses are transient, terminating within 8 h, while other synapses are much more stable. Relatively stable and transient synaptic pairs could be identified prospectively based on the strength of evoked transmission across the retina-muscle synapse.


STAT5A reprograms fatty acid metabolism and promotes tumorigenesis of gastric cancer cells.
The aim of this study was to determine the underlying effect of STAT5A-mediated fatty acid metabolism on the tumorigenesis of gastric cancer cells. The expression patterns of STAT5A and FASN in gastric cancer were investigated based on the Cancer Genome Atlas (TCGA) database and compared between 40 pairs of cancer samples and adjacent tissues. The pathological significance of STAT5A in gastric cancer was explored by GESA assay, and the molecular mechanism of STAT5A-mediated FASN expression was investigated by Luciferase assay and ChIP-qPCR. Fatty acid metabolic change was explored by detecting the content of neutral lipid, triglycerides, and phospholipids in STAT5A silenced MKN28 and AGS cells. Furthermore, Cell Counting Kit-8 (CCK-8) assay, colony formation, and Mouse xenograft were used to detect the function of STAT5A-mediated fatty acid metabolism on tumorigenic ability of gastric cancer cells. Upregulated STAT5A in gastric cancer was found to be not only an unconventional risk for over survival of gastric cancer patients, but also associated with fatty acid metabolism signaling. Furthermore, STAT5A can regulate the expression of the fatty acid binding protein 5 (FABP5) by binding to the promoter of FABP5 in MKN28 and AGS cells. Functional studies have shown that STAT5A-dependent FABP5 expression promoted the proliferation and tumorigenesis of gastric cancer cells by reprogramming intracellular fatty acid metabolism. Our results indicate that STAT5A-dependent FABP5 expression plays a carcinogenic role in the tumorigenesis of gastric cancer cells via reprogramming intracellular fatty acid metabolism, which establishes a new mechanism for the tumorigenesis of gastric cancer cells.


Stimulation of fat accumulation in hepatocytes by PGE₂-dependent repression of hepatic lipolysis, β-oxidation and VLDL-synthesis.
Hepatic steatosis is recognized as hepatic presentation of the metabolic syndrome. Hyperinsulinaemia, which shifts fatty acid oxidation to de novo lipogenesis and lipid storage in the liver, appears to be a principal elicitor particularly in the early stages of disease development. The impact of PGE₂, which has previously been shown to attenuate insulin signaling and hence might reduce insulin-dependent lipid accumulation, on insulin-induced steatosis of hepatocytes was studied. The PGE₂-generating capacity was enhanced in various obese mouse models by the induction of cyclooxygenase 2 and microsomal prostaglandin E-synthases (mPGES1, mPGES2). PGE₂ attenuated the insulin-dependent induction of SREBP-1c and its target genes glucokinase and fatty acid synthase. Nevertheless, PGE₂ enhanced incorporation of glucose into hepatic triglycerides synergistically with insulin. This was most likely due to a combination of a PGE₂-dependent repression of (1) the key lipolytic enzyme adipose triglyceride lipase, (2) carnitine-palmitoyltransferase 1, a key regulator of mitochondrial β-oxidation, and (3) microsomal transfer protein, as well as (4) apolipoprotein B, key components of the VLDL synthesis. Repression of PGC1α, a common upstream regulator of these genes, was identified as a possible cause. In support of this hypothesis, overexpression of PGC1α completely blunted the PGE₂-dependent fat accumulation. PGE₂ enhanced lipid accumulation synergistically with insulin, despite attenuating insulin signaling and might thus contribute to the development of hepatic steatosis. Induction of enzymes involved in PGE₂ synthesis in in vivo models of obesity imply a potential role of prostanoids in the development of NAFLD and NASH.


The effect of carbonyl group in the asymmetry of 3,4JCH coupling constants in norbornanones.
A rationalization of the known difference between the 3,4JC4H1 and 3,4JC1H4 couplings transmitted mainly through the 7-bridge in norbornanone is presented in terms of the effects of hyperconjugative interactions involving the carbonyl group. Theoretical and experimental studies of 3,4JCH couplings were carried out in 3-endo- and 3-exo-X-2-norbornanone derivatives (X = Cl, Br) and in exo- and endo-2-noborneol compounds. Hyperconjugative interactions were studied with the natural bond orbital (NBO) method. Hyperconjugative interactions involving the carbonyl pi*(C2=O) and sigma*(C2=O) antibonding orbitals produce a decrease of three-bond contribution to both 3,4JC4H1 and 3,4JC1H4 couplings. However, the latter antibonding orbital also undergoes a strong sigmaC3--C4 --> sigma*(C2=O) interaction, which defines an additional coupling pathway for 3,4JC4H1 but not for 3,4JC1H4. This pathway is similar to that known for homoallylic couplings, the only difference being the nature of the intermediate antibonding orbital; i.e. for 3,4JC4H1 it is of sigma*-type, while in homoallylic couplings it is of pi*-type.


Successful treatment of pudendal neuralgia with tricolumn spinal cord stimulation: case report.
There is large variation in the success of decompressive surgery for pudendal neuralgia (PN), the most chronic, disabling form of perineal pain. We attempt to determine whether spinal cord stimulation using new-generation multicolumn leads could form part of the treatment algorithm for refractory PN. A man with PN that was unresponsive to conventional treatment demonstrated a neuropathic component and had a negative response to nerve infiltrations (so he was not indicated for decompressive surgery) and a positive response to perianal transcutaneous electrical nerve stimulation and was implanted with a 16-contact surgical lead at the level of conus medullaris, allowing multicolumn stimulation. Using transverse combinations, it was possible to obtain 100% paresthesia over the perineal area without unwanted dorsal root stimulation. Perineal and radicular pain was successfully relieved for up to 12 months (80% and 60% reduction in the visual analogue scale scores, respectively), with an improvement in all quality of life domains and a reduction in drug consumption. Spinal cord stimulation using a 16-contact lead may be a viable therapeutic option for patients with refractory PN for whom decompressive surgery is contraindicated.


Genetic determination of Colles' fracture and differential bone mass in women with and without Colles' fracture.
Osteoporotic fractures (OFs) are a major public health problem. Direct evidence of the importance and, particularly, the magnitude of genetic determination of OF per se is essentially nonexistent. Colles' fractures (CFs) are a common type of OF. In a metropolitan white female population in the midwestern United States, we found significant genetic determination of CF. The prevalence (K) of CF is, respectively, 11.8% (+/- SE 0.7%) in 2471 proband women aged 65.55 years (0.21), 4.4% (0.3%) in 3803 sisters of the probands, and 14.6% (0.7%) in their mothers. The recurrence risk (K0), the probability that a woman will suffer CF if her mother has suffered CF is 0.155 (0.017). The recurrence risk (Ks), the probability that a sister of a proband woman will suffer CF given that her proband sister has suffered CF is 0.084 (0.012). The relative risk lambda (the ratio of the recurrence risk to K), which measures the degree of genetic determination of complex diseases such as CF, is 1.312 (0.145; lambda 0) for a woman with an affected mother and 1.885 (0.276; lambda s) for a woman with an affected sister. A lambda-value significantly greater than 1.0 indicates genetic determination of CF. The terms lambda 0 and lambda s are related to the genetic variances of CF. These parameters translate into a significant and moderately high heritability (0.254 [0.118]) for CF. These parameters were estimated by a maximum likelihood method that we developed, which provides a general tool for characterizing genetic determination of complex diseases. In addition, we found that women without CF had significantly higher bone mass (adjusted for important covariates such as age, weight, etc.) than women with CF.


Photobiology of natural populations of zooxanthellae from the sea anemone Aiptasia pallida: assessment of the host's role in protection against ultraviolet radiation.
Natural populations of the sea anemone Aiptasia pallida containing endosymbiotic dinoflagellates were acclimated to different irradiance regimes, with and without ultraviolet radiation (UV). They showed a compensatory response in the amount of chlorophyll and the activities of enzymes responsible for detoxifying active species of oxygen that are produced by the interaction between visible or ultraviolet radiation and photosynthetically produced oxygen. Protection from active species of oxygen is essential to prevent the photooxidation of chlorophyll and the concomitant loss of productivity. Bulk analyses of chlorophyll showed differences between the populations exposed to varying irradiance regimes, but revealed no significant independent effect of UV. However, analysis by flow cytometry of the individual cells from treated populations did detect statistically significant differences in cell size and the amount of chlorophyll fluorescence per cell, which could be attributed to treatment with ultraviolet radiation. With flow cytometry we are able to detect the population variability that is undetectable by bulk measurements which is important in assessing the effects of environmental parameters in both symbiotic and free-living microalgae. Research using simultaneous measurements by flow cytometry could add considerable insight into the population dynamics of both zooxanthellae and host cells.


Heat production and respiratory enzymes in normal and runt newborn piglets.
The heat productions of newborn runt and normal piglets were estimated over a range of ambient temperatures. Most runts increased their heat production in the cold, but when expressed as J X kg-0.67 X min-1 it was significantly lower than in normal piglets (201.3 +/- 16.0 and 144.7 +/- 16.2 J X kg-0.67 X min-1 for controls and runts, respectively, at 32 degrees C). Runts consequently had lower deep body temperatures (37.8 +/- 0.2 and 36.8 +/- 0.3 degrees C for controls and runts, respectively, at 32 degrees C). Some runts failed to increase their metabolic rate in the cold and these had the lowest deep body temperature. Activities of respiratory enzymes in heart and diaphragm muscle were similar in all animals, whereas the longissimus dorsi of runts had significantly lower enzyme activities (76.3 +/- 4.2 and 55.5 +/- 6.6 in absorbance units for controls and runts, respectively).


Lipomatosis and true lipomas of the ileocecal valve.
Two patients with lipomatosis and two patients with true lipoma of the ileocecal valve are described. The symptomatology, radiological appearances, pathological findings and treatment are discussed. True lipomas of the ileocecal valve should be differentiated from the more commonly occurring lipomatosis or lipohyperplasia. The rare true lipomas have a demarcating capsule around the fatty tissue and are confined to only one of the ileocecal lips. The lipomatosis, on the other hand, is characterized by a diffus fatty deposition in the submucosa of the valve with no encapsulation. Lipomatosis as well as true lipomas may appear as rounded, smoothly outlined and sharply demarcated masses on barium enema examination. Occasionally, these filling defects may present problems of differential diagnosis with respect to malignant involvement of the ileocecal region. A correct preoperative diagnosis, however, is important to prevent unnecessary or too radical surgical treatment.


Opening the window: Size of the attentional window dominates perceptual load and familiarity in visual selection.
Perceptual load theory (Lavie, 1995) claims that visual selection is determined both by the perceptual demands a display imposes and by the perceptual resources an observer has available for processing. This theory is often tested by examining distractor interference in modified flanker tasks, which separate potential target locations from distractor locations and allow researchers to measure distractor processing. Although this task has provided significant insight into cognitive processing, it may also be an example of how a given task obscures potentially important experimental factors. Specifically, the structure of the target array could encourage observers to adopt a narrow attentional window, which could eliminate distractor interference as significant distractor processing has been shown to occur inside but not outside the attentional window (Belopolsky, Zwaan, Theeuwes, & Kramer, 2007). The present experiments included conditions that allowed the target to vary among the same locations as within a structured target array but varied possible nontarget locations that never overlapped with possible target locations. Whenever nontarget items remained in fixed locations, significant distractor processing occurred due to the observer adopting a wide attentional window even under high perceptual load conditions (Experiment 1). Further evidence showed that familiarity with these locations could not explain the interference (Experiment 2A). However, imposing a ring around the target array, similar to what a circular target array might impose, narrowed the attentional window and eliminated distractor interference (Experiment 2B). Thus, the size of the attentional window is capable of dominating both perceptual load and familiarity in visual selection. (PsycINFO Database Record (c) 2018 APA, all rights reserved).


High risk squamous cell carcinoma.
Mrs MA, 70 years of age, has a history of scalp psoriasis dating over 10 years. She explained that the rash was slowly progressing and had failed to respond to an array of topical treatments offered. Within the right lateral aspect of the 12 x 14 cm lesion a thick nodule had recently developed. It looked like squamous cell carcinoma (SCC). Biopsy of the raised lesion confirmed SCC as did four other biopsies at the poles of the region of 'psoriasis'. Removing all surface debris confirmed this was one confluent scalp tumour. The large scalp SCC was excised with a 5 mm margin. During surgery there was an area of apparent involvement of galea. This layer was widely excised along with periosteum at that point. Histology confirmed complete excision. There was no other point at which deep levels were involved. Periosteum was not involved. The large defect was closed with a partial thickness skin graft harvested from the right anterior thigh.


Total synthesis of the Fusarium toxin equisetin.
A short stereoselective synthesis of the Fusarium toxin equisetin, a potent inhibitor of HIV-1 integrase enzyme is described, using as the key step a stereoselective intramolecular Diels-Alder reaction of a fully conjugated E,E,E-triene with a trisubstituted gamma,delta-unsaturated beta-ketothioester.


5-Lipoxygenase and leukotriene synthesis: effects of calcium ions and of inhibitors.
5-Lipoxygenase and leukotriene (LT) A4 synthase, the first two enzymes in the pathway converting arachidonic acid to leukotrienes, can be co-purified. The Ca2+-activated conversion of arachidonic acid and of 5-hydroperoxyeicosatetraenoic acid (5-HPETE) to LTB4 have been compared, using cytosol from human leucocytes. The two activities showed identical responses to a number of inhibitors, suggesting that the two catalytic activities may involve the same active centre. The effects of Ca2+ ions were further investigated. With 5-HPETE as substrate, substantial synthesis of LTB4 was given in the absence of Ca2+, and the inhibitor sensitivity of this component was quite different from that of the Ca2+-activated component. This Ca2+-independent synthase activity was, however, very low in saponin-permeabilised washed leucocytes and it may therefore be not significant physiologically. With arachidonic acid as substrate at pH 7, the activity was highly Ca2+-dependent at a low substrate concentration (6.6 microM), but at a high concentration (132 microM) substantial activity was observed without Ca2+. This was also found when 5-lipoxygenase was assayed in cytosol from RBL cells. At pH 8-8.5, however, Ca2+ was required at both high and low concentrations of arachidonic acid. This suggests that Ca2+ is required for 5-lipoxygenase activity on arachidonate ions in solution but possibly not on protonated arachidonic acid or micelles.


Regulation of cotton (Gossypium hirsutum) drought responses by mitogen-activated protein (MAP) kinase cascade-mediated phosphorylation of GhWRKY59.
Drought is a key limiting factor for cotton (Gossypium spp.) production, as more than half of the global cotton supply is grown in regions with high water shortage. However, the underlying mechanism of the response of cotton to drought stress remains elusive. By combining genome-wide transcriptome profiling and a loss-of-function screen using virus-induced gene silencing, we identified Gossypium hirsutum GhWRKY59 as an important transcription factor that regulates the drought stress response in cotton. Biochemical and genetic analyses revealed a drought stress-activated mitogen-activated protein (MAP) kinase cascade consisting of GhMAP3K15-Mitogen-activated Protein Kinase Kinase 4 (GhMKK4)-Mitogen-activated Protein Kinase 6 (GhMPK6) that directly phosphorylates GhWRKY59 at residue serine 221. Interestingly, GhWRKY59 is required for dehydration-induced expression of GhMAPK3K15, constituting a positive feedback loop of GhWRKY59-regulated MAP kinase activation in response to drought stress. Moreover, GhWRKY59 directly binds to the W-boxes of DEHYDRATION-RESPONSIVE ELEMENT-BINDING PROTEIN 2 (GhDREB2), which encodes a dehydration-inducible transcription factor regulating the plant hormone abscisic acid (ABA)-independent drought response. Our study identified a complete MAP kinase cascade that phosphorylates and activates a key WRKY transcription factor, and elucidated a regulatory module, consisting of GhMAP3K15-GhMKK4-GhMPK6-GhWRKY59-GhDREB2, that is involved in controlling the cotton drought response.


Synthesis and biological activity of some cardiotonic compounds related to gitoxigenin.
The four diastereomeric 3,16-diacetates 6, 9, 10 and 11 were prepared from gitoxin 1 by the routes shown in Schemes 1 and 2 and tested for inotropic activity in the isolated guinea-pig atrial preparation. In line with earlier findings in the digitoxigenin series, derivatives with a 3 alpha-acetoxy function, viz 9 and 10, possessed high biological activity.


[Complex formation between trigliceropeptides pseudomonades and plant root exudates as a mechanism of action on phytopathogens].
The influence of plant exudates on the antifungal activity of Pseudomonas chlororaphis strains (BI 6, BI 51) and P. putida (BI 17) was investigated in model experiments. Using UV spectroscopy and polarimetry methods, triglyceropeptide metabolites from the Pseudomonas strain were shown to form intermolecular complexes with plant exudates such as carbohydrates, organic acids, and amino acids. The stoichiometric contents of metabolite-exudate complexes were evaluated.


The transcription factor HACA mediates the unfolded protein response in Aspergillus niger, and up-regulates its own transcription.
The unfolded protein response (UPR) involves a complex signalling pathway in which the transcription factor HACA plays a central role. Here we report the cloning and characterisation of the hacA gene and its product from Aspergillus niger. ER (endoplasmic reticulum) stress results in the splicing of an unconventional 20-nt intron from the A. niger hacA mRNA, and is associated with truncation of the 5'-end of the hacA mRNA by 230 nt. In this study the UPR was triggered by over expressing tissue plasminogen activator (t-PA), and by treatment of mycelia with dithiothreitol (DTT) or tunicamycin. Overexpression of the processed form of hacA not only led to the up-regulation of bipA, cypB and pdiA--mimicking the UPR--but also led to the up-regulation of the hacA gene itself. In vitro binding assays confirmed that the HACA protein binds to the promoters of genes encoding ER-localised chaperones and foldases, and to the promoter of the hacA gene itself. Finally, a GFP-HACA fusion was shown to localise in the nucleus.


Physicochemical, rheological and structural characteristics of starch in maize tortillas.
Fresh and stored maize (white and blue) tortillas were evaluated for physicochemical, rheological and structural characteristics assessed by calorimetry, x-ray diffraction, Fourier transform infrared (FTIR) spectroscopy, dynamic viscoelastic tests, and high-performance size-exclusion chromatography. Two endotherms were found in studies of fresh and stored tortillas. The low temperature endotherm (50-56 degrees C) was due to reorganized (retrograded) amylopectin, while the high temperature endotherm (105-123 degrees C) was attributed to retrograded amylose. The enthalpy value for the lower temperature transition was minor than that of the high temperature transition. Fresh tortillas showed an amorphous starch arrangement by x-ray diffraction study. Stored samples showed the presence of peaks at 2theta = 17 masculine and 23 masculine, indicating re-crystallization of starch components. FTIR results confirmed the development of higher levels of starch crystals during storage. Differences in the viscoelastic parameters were also observed between fresh and stored samples. At the longest storage times, white tortillas were more rigid than blue tortillas. Molar mass values for starch increased for both white and blue tortillas as storage time progressed, though relatively higher values were obtained for white tortillas. More starch reorganization occurred in white tortillas, in accordance to calorimetric, x-ray diffraction, FTIR and rheological results. These results corroborate that changes occurring in tortillas during storage are related to reorganization of starch components, and the maize variety more than the color plays an important role.


The effect of single-pass reaming on tibial nail insertion load and stress.
This biomechanical study evaluated and compared the longitudinal and perpendicular stresses generated and the applied load required during the insertion of a tibial nail with three different insertion techniques. Insertion of a narrow-diameter nail using an unreamed technique generated significantly greater stress and required significantly greater applied load than either the single-pass reamed technique or a reamed technique. The single-pass reamed technique and the standard reamed technique were not significantly different from each other. This study biomechanically justifies the use of the single-pass reaming technique during the insertion of a narrow-diameter intramedullary nail in severe open tibial fractures. The use of this technique cannot be advocated until the biologic effect of single-pass reaming is more clearly defined.


Unusual ligand transformations initiated by dppm deprotonation in methylene-bridged Rh/Os complexes.
The reaction of [RhOs(CO)(3)(μ-CH(2))(dppm)(2)][CF(3)SO(3)] (dppm = μ-Ph(2)PCH(2)PPh(2)) with 1,3,4,5-tetramethylimidazol-2-ylidene (IMe(4)) results in competing substitution of the Rh-bound carbonyl by IMe(4) and dppm deprotonation by IMe(4) to give the two products [RhOs(IMe(4))(CO)(2)(μ-CH(2))(dppm)(2)][CF(3)SO(3)] and [RhOs(CO)(3)(μ-CH(2))(μ-κ(1):η(2)-dppm-H)(dppm)] [3; dppm-H = bis(diphenylphosphino)methanide], respectively. In the latter product, the dppm-H group is P-bound to Os while bound to Rh by the other PPh(2) group and the adjacent methanide C. The reaction of the tetracarbonyl species [RhOs(CO)(4)(μ-CH(2))(dppm)(2)][CF(3)SO(3)] with IMe(4) results in the exclusive deprotonation of a dppm ligand to give [RhOs(CO)(4)(μ-CH(2))(μ-κ(1):κ(1)-dppm-H)(dppm)] (4) in which dppm-H is P-bound to both metals. Both deprotonated products are cleanly prepared by the reaction of their respective precursors with potassium bis(trimethylsilyl)amide. Reversible conversion of the μ-κ(1):η(2)-dppm-H complex to the μ-κ(1):κ(1)-dppm-H complex is achieved by the addition or removal of CO, respectively. In the absence of CO, compound 3 slowly converts in solution to [RhOs(CO)(3)(μ-κ(1):κ(1):κ(1)-Ph(2)PCHPPh(2)CH(2))(dppm)] (5) as a result of dissociation of the Rh-bound PPh(2) moiety of the dppm-H group and its attack at the bridging CH(2) group. Compound 4 is also unstable, yielding the ketenyl- and ketenylidene/hydride tautomers [RhOs(CO)(3)(μ-κ(1):η(2)-CHCO)(dppm)(2)] (6a) and [RhOs(H)(CO)(3)(μ-κ(1):κ(1)-CCO)(dppm)(2)] (6b), initiated by proton transfer from μ-CH(2) to dppm-H. Slow conversion of these tautomers to a pair of isomers of [RhOs(H)(CO)(3)(μ-κ(1):κ(1):κ(1)-Ph(2)PCH(COCH)PPh(2))(dppm)] (7a and 7b) subsequently occurs in which proton transfer from a dppm group to the ketenylidene fragment gives rise to coupling of the resulting dppm-H methanide C and the ketenyl unit. Attempts to couple the ketenyl- or ketenylidene-bridged fragments in 6a/6b with dimethyl acetylenedicarboxylate (DMAD) yield [RhOs(κ(1)-CHCO)(CO)(3)(μ-DMAD)(dppm)(2)], in which the ketenyl group is terminally bound to Os.


Production of tissue inhibitor of metalloproteinase-1 and -2 by cultured keratinocytes.
The imbalance between metalloproteinases and their inhibitors in tissue remodelling is likely to play an important role in various pathologic conditions. In order to understand the role of keratinocytes in regulating extracellular matrix degradation in skin, we analyzed the production of metalloproteinase inhibitors in keratinocytes. Tissue inhibitor of metalloproteinase-1 (TIMP-1) and tissue inhibitor of metalloproteinase-2 (TIMP-2) mRNA were detected in cultured human keratinocytes and mouse transformed keratinocyte cell line (KCMH-1) cells by RT-PCR. On several column chromatography separation steps of the KCMH-1 conditioned medium, two specific inhibitors for mammalian collagenase were purified showing an Mr of 29 kDa and an Mr of 22 kDa, respectively. The analysis of their N-terminal amino acid sequence revealed that two inhibitors were TIMP-1 and TIMP-2. The final preparation of TIMP-1 had a specific activity of 56000 U/mg and that of TIMP-2 had a specific activity of 26200 U/mg. Our results suggest that keratinocytes take part in tissue remodelling in skin in secreting both TIMP-1 and TIMP-2.


Imaging transcription complexes with the Atomic Force Microscope.
Recent developments in sample deposition and image analysis have shown that the Atomic Force Microscope is a valuable tool for the structural investigation of transcription complexes. When deposited under conditions that allow molecular equilibration onto the substrate, transcription complexes behave as worm-like chains and the mean square end-to-end distance can readily be used to determine the protein induced DNA bend angle. Measurements of the DNA contour length by means of accurate image processing procedures have revealed a DNA compaction in transcription complexes which is compatible with wrapping of the DNA against the surface of the RNA Polymerase. The methods presented have to be considered of general practical use for imaging protein-DNA complexes.


Apoptotic and inflammatory cytokine protein expression in intestinal lymphocytes after acute treadmill exercise in young and old mice.
Gastrointestinal disturbances are common in athletes following intense exercise. Variations in apoptotic protein expression and cell death may contribute to acute exercise-induced intestinal inflammation. The effect of age on apoptotic protein response in the intestinal compartment in response to exercise is not known. Using a mouse model, we examined the effects of a single bout of treadmill running in young and old mice on intestinal lymphocyte (IL) expression of the apoptosis-inducing cytokine TNF-α, the pro-apoptotic proteins caspase-3 and 7, the anti-apoptotic protein Bcl-2, and IL apoptotic status (% AnnexinV+). Young (3-4 months, N.=44) and old (13-14 months, N.=45) female C57Bl/6 mice were randomized to treadmill exercise (10 min warm-up, 20 min at 22 m min-1, 30 min at 25 m min-1, 30 min at 28 m min-1, 2º slope) with sacrifice immediately (IMM) or 2hr after (2Hr), or to a non-exercised control (SED). IL were removed and prepared for analysis of % apoptosis (flow cytometry) and determination of apoptotic protein and cytokine expression (Western blotting). Plasma corticosterone and 8-iso-PGF2α were measured by EIA. Exercise was associated with a higher IL expression of caspase-3 in IMM and 2Hr groups vs. SED (P<0.001), a higher expression of TNF-α in the IMM group vs. SED (P<0.001), and a lower Bcl-2 expression in the IMM and 2Hr groups vs. SED (P<0.01). There was a trend (P=0.07) for increased caspase-7 expression after exercise. IL caspase-3 and 7 and TNF-α expression did not differ by age whereas Bcl-2 expression was lower (P<0.001) and % Annexin V+ IL was higher (P<0.05) in old vs. young mice. Plasma corticosterone and 8-iso-PGF2α were higher (P<0.001 and P<0.05) in IMM vs. SED mice but did not differ by age. The expression of the pro-apoptotic proteins, caspase-3 and caspase-7, and the apoptosis-inducing cytokine, TNF-α, in IL did not differ by age in this animal model in response to a single intense exercise challenge. However, Old mice had lower expression of the 'protective' anti-apoptotic protein Bcl-2 and a higher percentage of early apoptotic IL. Whether repeated exercise results in less IL resiliency in elderly individuals remains to be determined.


Relaxation and complementary therapies: an alternative approach to managing dental anxiety in clinical practice.
Dental anxiety is a widespread problem and has a significant impact on the provision of dental care for the general population. Anxiety leads to avoidance of dental treatment and increased stress for dental practitioners. Traditionally, dental anxiety has been managed using pharmacological techniques. This article reviews alternative treatment approaches, including psychological and complementary therapies which can be used in managing dental anxiety and facilitating dental treatment. Many of these approaches are currently being used within the dental profession. Others are gaining a wider acceptance as to their usage. Where available, the evidence of their efficacy will be reviewed.


A RFID specific participatory design approach to support design and implementation of real-time location systems in the operating room.
Information technology, such as real-time location (RTL) systems using Radio Frequency IDentification (RFID) may contribute to overcome patient safety issues and high costs in healthcare. The aim of this work is to study if a RFID specific Participatory Design (PD) approach supports the design and the implementation of RTL systems in the Operating Room (OR). A RFID specific PD approach was used to design and implement two RFID based modules. The Device Module monitors the safety status of OR devices and the Patient Module tracks the patients' locations during their hospital stay. The PD principles 'multidisciplinary team', 'participation users (active involvement)' and 'early adopters' were used to include users from the RFID company, the university and the hospital. The design and implementation process consisted of two 'structured cycles' ('iterations'). The effectiveness of this approach was assessed by the acceptance in terms of level of use, continuity of the project and purchase. The Device Module included eight strategic and twelve tactical actions and the Patient Module included six strategic and twelve tactical actions. Both modules are now used on a daily basis and are purchased by the hospitals for continued use. The RFID specific PD approach was effective in guiding and supporting the design and implementation process of RFID technology in the OR. The multidisciplinary teams and their active participation provided insights in the social and the organizational context of the hospitals making it possible to better fit the technology to the hospitals' (future) needs.


Stage III Hodgkin's disease--long-term results following chemotherapy, radiotherapy and combined modality therapy.
215 patients with stage III Hodgkin's disease (HD) were treated at the Royal Marsden Hospital between 1963 and 1985 (median follow-up 9 years). The actuarial 5- and 10-year survival was 77 and 65%, respectively with 55 and 48% 5 and 10 year disease-free survival. Of 13 variables tested, age was the only independent prognostic indicator for survival on multivariate analysis. Patients aged under 40, 40-59 and over 60 years had a 10-year survival of 76, 41 and 8%, respectively (p much less than 0.001). Ninety-one patients were initially treated with combined chemotherapy and radiotherapy (combined modality therapy, CMT), 73 patients with radiotherapy (RT) and 51 patients with chemotherapy (CT) alone. Patients under 40 years treated with CMT achieved the best disease-free survival (10 year disease-free survival: CMT 68%; RT 38%; CT 45%). The observed survival advantage for CMT was not statistically significant. In patients aged greater than 40 there was no survival or disease-free survival advantage following CMT. Analysis of recurrence pattern confirmed that CMT improves initial disease control both at previously involved and uninvolved sites. Recurrences at previously uninvolved sites continued up to 6 years following CT, up to 8 years following CMT and up to 14 years after RT alone. These results indicate that only long-term follow-up gives the true picture of stage III HD.


Marginal adaptation, retention and fracture resistance of adhesive composite restorations on devital teeth with and without posts.
This in vitro study generated data on the quality of marginal adaptation, fracture resistance and retention of several indirect adhesive composite configurations on root-treated premolars before and after a long-term fatigue test and compared these results to a control group of adhesive onlays on "vital" teeth. Six root-treated extracted human premolars per group, with four different restorative configurations with and without adhesive fiber posts, were evaluated. Another group of six premolars, "revitalized" by using diluted horse serum to simulate pulpal fluid and restored with adhesive composite onlays, served as the control. Marginal adaptation before and after long-term occlusal loading (1,200,000 occlusal loading cycles at max 49 N) was assessed by using the replica technique and quantitative evaluation in SEM at 200x magnification. The number of lost restorations was recorded after loading. Fracture resistance and fracture patterns were evaluated by using a universal-testing machine on the fatigued samples. No significant differences (p > 0.05) between groups were detected before and after loading for the percentage of "continuous margin" at the total marginal length. Loading had a significant (p < 0.05) effect on the percentage of "continuous margin" for the total marginal length of two groups only. No significant difference (p > 0.05) for fracture resistance was detected and no lost restorations were observed. The results suggest that for both the less decayed and the more significantly decayed devital teeth, the minimally invasive adhesive restorative approach is promising.


Gout in systemic lupus erythematosus and overlap syndrome - a hospital-based study.
The negative association between gout and rheumatoid arthritis is widely accepted, and gout is also speculated to be rare in systemic lupus erythematosus (SLE), as only a few sporadic cases have been reported. From 1985 to 2001 we encountered 15 lupus patients at Chang-Gung Memorial Hospital, including two with lupus-scleroderma and one with lupus-scleroderma-polymyositis overlap syndrome coexisting with gout. This study retrospectively analyses the clinical and laboratory characteristics of these patients. A lower female predominance is found, and most patients developed gout after the onset of SLE, although gout preceded SLE in two cases. Measurement of serum uric acid and 24-h urine uric acid found all of the patients to be hyperuricaemic and underexcretors of uric acid. Furthermore, most of the patients (14/15) were receiving diuretics. Also, many had hypertension and serious cardiovascular diseases. Renal impairment during gouty attacks seemed to be a predisposing factor for developing end-stage renal disease. Gouty arthritis usually occurred during relative SLE inactivity, podagra was frequent, and tophi were found in a few patients. Compared with the unselected population of SLE patients, the cases studied here had a higher incidence of chronic arthritis, malar rash, haematologic disorder, photosensitivity, serositis and neurologic disorder. Renal disease in the patients sampled was frequently membranous nephropathy.


Postnatal exposure to low-dose bisphenol A influences various emotional conditions.
Bisphenol A (BPA) is one of the 'environmental endocrine disrupters' (EEDs) released by plastics and resin known to interfere with hormonal responses. In this study, female Wistar rats were exposed to low-dose BPA (24 μg/kg/day) during 7 days after giving birth. The male and female offspring, exposed to the BPA through lactation, were evaluated using an open field test (OFT) at the age of six weeks, an elevated plus maze test (EPM) at seven weeks, and a forced swimming test (FST) at nine weeks. The OFT indicated that females were more active than males, and that BPA selectively increased rearing duration in males, thereby eliminating the gender effect. The results of EPM showed that BPA did not enhance the anxiety-like action; rather, it was associated with an anxiolytic-like action in females. In the FST, not only there was an increase in the immobility time, but also there was reduction of latency observed in BPA rats. It indicated that the depression-like responses were clearly enhanced by the postnatal exposure. Altogether, these data suggest that low-dose BPA ingested by neonates through breastfeeding may cause persistent aberrant behaviors that are relevant to emotions.


Does electroconvulsive therapy (ECT) have any role in the management of intractable thalamic pain?
Three patients with intractable thalamic pain unresponsive to a range of previous treatments received a course of six bilateral electroconvulsive therapy (ECT) treatments over 2 weeks. There was no evidence of any improvement in the intensity of the pain, pain relief or mood as measured on visual analogue scales and with standard measures. Propofol was used as the anaesthetic induction agent. Two patients showed wide changes in blood pressure during ECT but all three patients showed prompt recovery. In the light of the negative findings of this study and those of a previous study of the use of unilateral ECT in similar patients it is concluded that ECT is not an effective treatment for post-stroke thalamic pain.


Treatment of hepatitis C virus infection in patients of northern India.
The purpose of the present study was to evaluate the therapeutic response of north Indian patients with chronic hepatitis C (CH-C) to two different treatment regimens of interferon and ribavirin. Consecutive patients with a diagnosis of CH-C attending the Liver Clinic at the All India Institute of Medical Sciences, New Delhi between April 1999 and April 2002 were included in the study. A competitive reverse transcription-polymerase chain reaction (RT-PCR) method developed in the authors' laboratory was used for quantification of hepatitis C virus (HCV)-RNA. Genotyping of HCV was also determined. The clinical, biochemical, virological and histological parameters were used to assess the therapeutic response among a clinical cohort of patients with chronic hepatitis C. They were treated with two different protocols (interferon [IFN]-alpha-2b, 3 million units daily and ribavirin 10.6 mg/kg daily in two divided doses for 6 months or IFN-alpha-2b, 3 million units thrice weekly and ribavirin 10.6 mg/kg daily for 6 months). Sixty-five patients with CH-C were included in the study. Blood transfusion (n = 28, 43%) and community-acquired (n = 23, 35%) HCV infections were the commonest. The mean HCV load was high (24.14 +/- 12.5 x 10(8) copies/mL). Genotype 2 and 3 were prevalent in 80% (41/51) of the patients. Forty-five patients received 3 million units of IFN thrice weekly and 20 received the same dose daily. All received the same dose of ribavirin. A sustained virological response (SVR) of 95% (19/20) was achieved among patients receiving daily IFN, whereas 64.4% (29/45) of those who received IFN thrice weekly had SVR. The virological relapse was significantly lower among patients who received daily IFN than in those treated with thrice weekly IFN (n = 1/20, 5% vs 10/39, 25.6%; P = 0.015). The proportion of patients receiving daily IFN among those achieving SVR (19/48, 40%) was significantly higher than the proportion of patients receiving similar therapy among patients without SVR (1/17, 6%; P = 0.02). Transfusion and community-acquired HCV infection were the major causes of CH-C. Genotype 2 and 3 HCV were most prevalent among these patients. Despite high viral load, these patients responded well to a combination of daily IFN-alpha-2b and ribavirin.


Evaluation of the effect of radiotherapy for pituitary tumours on cognitive function and quality of life.
Pituitary tumours are often treated with radiotherapy, which can cause cognitive impairment when given in high doses. It is assumed that current regimens do not cause damage, but this has not been established. The aim was to determine whether radiotherapy given to people with pituitary tumours was associated with cognitive impairment and reduced quality of life. We retrospectively compared two outcome groups (patients with pituitary tumours who had undergone radiotherapy and surgery and patients with pituitary tumours who had surgery alone), and carried out standardised tests of cognitive function and quality of life. The data suggested that patients with pituitary tumours treated with surgery, with or without radiotherapy, had cognitive impairment compared with the normal population. Patients receiving radiotherapy performed significantly worse than those receiving only surgery on the Stroop test, a measure of executive function. They also scored significantly lower on the Physical Health composite of the SF36, although this difference was no longer significant when account was taken of baseline differences between the groups. There were no significant differences in other cognitive functions, mood, general well-being or the Mental Health Composite of the SF36. Patients treated for pituitary disease may have cognitive impairment. A decrease in cognitive function was found regardless of treatment type. The decrease seemed to be greater in the radiotherapy group and was mainly on executive function. This impairment of executive function could affect daily life. Further prospective studies are required to assess the effect of pituitary disease on cognitive function and the safety of radiotherapy.


[System for intraoral repair of ceramic blends--an in vitro study of adhesive strength].
We investigated composite repair systems for crown facings which consisted in principle of a silane primer, of an unfilled Bis-GMA bonding agent and of a filled Bis-GMA resin. The in vitro investigations revealed that under oral conditions the longterm durability of the bond strength is still unsufficient, unless care is taken that the debris layer which is caused by mechanical treatment has been removed.


Controlled synthesis of biodegradable lactide polymers and copolymers using novel in situ generated or single-site stereoselective polymerization initiators.
Polylactides and their copolymers are key biodegradable polymers used widely in biomedical, pharmaceutical and ecological applications. The development of synthetic pathways and catalyst/initiator systems to produce pre-designed polylactides, as well as the fundamental understanding of the polymerization reactions, has continuously been an important topic. Here, we will address the recent advances in the ring-opening polymerization of lactides, with an emphasis on the highly versatile in situ generated initiator systems and single-site stereoselective initiators. The in situ generated initiators including in situ formed yttrium, calcium and zinc alkoxides all have been shown to bring about a rapid and living polymerization of lactides under mild conditions, which facilitated the preparation of a variety of advanced lactide-based biomaterials. For example, well-defined di- and tri-block copolymers consisting of hydrophilic poly(ethylene glycol) blocks and hydrophobic polyester blocks, which form novel biodegradable polymersomes or biodegradable thermosensitive hydrogels, have been prepared. In the past few years, significant progress has also been made in the area of stereoselective polymerization of lactides. This new generation of initiators has enabled the production of polylactide materials with novel microstructures and/or properties, such as heterotactic (--RRSSRRSSRRSS--) polylactide, crystalline syndiotactic (--RSRSRSRSRSRS--) polylactide and isotactic stereoblock (--Rn Sn Rn Sn--) polylactide, exhibiting a high melting temperature. The recently developed polymerizations using in situ generated initiators and stereoselective polymerizations have no doubt opened a brand-new avenue for the design and exploration of polylactides and their copolymers.


1.3-A resolution structure of human glutathione S-transferase with S-hexyl glutathione bound reveals possible extended ligandin binding site.
Cytosolic glutathione S-transferases (GSTs) play a critical role in xenobiotic binding and metabolism, as well as in modulation of oxidative stress. Here, the high-resolution X-ray crystal structures of homodimeric human GSTA1-1 in the apo form and in complex with S-hexyl glutathione (two data sets) are reported at 1.8, 1.5, and 1.3A respectively. At this level of resolution, distinct conformations of the alkyl chain of S-hexyl glutathione are observed, reflecting the nonspecific nature of the hydrophobic substrate binding site (H-site). Also, an extensive network of ordered water, including 75 discrete solvent molecules, traverses the open subunit-subunit interface and connects the glutathione binding sites in each subunit. In the highest-resolution structure, three glycerol moieties lie within this network and directly connect the amino termini of the glutathione molecules. A search for ligand binding sites with the docking program Molecular Operating Environment identified the ordered water network binding site, lined mainly with hydrophobic residues, suggesting an extended ligand binding surface for nonsubstrate ligands, the so-called ligandin site. Finally, detailed comparison of the structures reported here with previously published X-ray structures reveal a possible reaction coordinate for ligand-dependent conformational changes in the active site and the C-terminus.


[Pili determined by the tra genes of F-like plasmids].
The study of structural and functional features of plasmid-specific pili synthetized by E. coli cells under control of 27 F-like plasmids was performed. All the plasmids determined the pili of "flexible" type which were classified into 3 groups on the basis of difference in cell sensitivity to pili-specific phages f1, f2, Q. The possible role of transposons in the variation of pili functional properties was supposed.


Differentiating genomics companies.
As the value of raw sequence data diminishes, genomics companies are evolving new competencies as providers of information, therapeutic products, or novel technology.


Current laboratory assays and in vitro intracellular Th1 and Th2 cytokine synthesis in monitoring antiretroviral therapy of pediatric HIV infection.
In 42 HIV-infected children, 8-10 years old, belonging to the category A state of infection, combined antiretroviral therapy (cART) was applied, consisting of AZT, ddC and Saquinavir. At 6 and 12 weeks following the start of cART, the efficacy of treatment was assessed, both by means of current parameters (blood CD4+ cell levels, virus load) and by measuring the intracellular synthesis of some Th1 (interleukin (IL)-2, interferon-gamma) and Th2 (IL-4, IL-10) cytokines, in CD4+ lymphocytes, respectively. Before cART, low values of blood CD4+ cell counts and a mean of about 8000 virus RNA copies ml(-1) of serum were detected, and in addition decreased levels of production of both intracellular Th1 cytokines, associated with increased levels of one of the Th2 cytokines (IL-10), but not of the other (IL-4), were noticed. After cART, earlier improvement of intracellular IL-2, interferon-gamma and IL-10 synthesis in CD4+ cells occurred compared to CD4+ counts and virus load. The usefulness of scoring the rates at which CD4+ lymphocytes are able to synthesize intracellular Th1 or Th2 cytokines, as an additional immune parameter during combined antiretroviral therapy monitoring in pediatric AIDS, is discussed.


Adjunctive diagnostic value of MRI in the breast radial scar.
We sought to identify breast magnetic resonance imaging (MRI) criteria capable of influencing the differential diagnosis between radial scars related to benign proliferative disease and those associated with breast cancer with a view to proposing breast MRI as a promising and cost-effective modality to be carried out between mammography and surgical biopsy. From 1998 to June 2006, we studied 20 patients with a focal architectural distortion on mammography. All patients underwent contrast-enhanced breast MRI with a T1 Philips Gyroscan scanner and the acquisition of T1-weighted fast field echo, echo planar imaging (FFE EPI) axial dynamic sequences with a slice thickness of 3 mm. During postprocessing, subtracted images were assessed for morphological features, pattern of contrast enhancement, time-intensity curve and lesion enhancement rate. Breast MRI depicted 27 lesions between 7 mm and 30 mm in size. Fifteen of the 27 breast lesions showed benign features, eight showed malignant features and four were classified as suspicious. Pathological examination confirmed the benignity of all 15 lesions showing benign MRI features and revealed the benign nature of the four lesions classified as suspicious. Evaluation of breast MRI showed that enhancement rate and time-intensity curve were useful only in the differential diagnosis between benign and malignant breast lesions. Our experience confirmed that breast MRI has very high sensitivity and, in particular, a negative predictive value of 100%. Breast MRI could thus be considered a useful diagnostic tool that can guide the choice between follow-up or surgical excision of radial scars.


Mutational analysis of conserved amino acids in the T cell receptor alpha-chain transmembrane region: a critical role of leucine 112 and phenylalanine 127 for assembly and surface expression.
Correct assembly of all TCR complex polypeptides is essential for its cell surface expression and function. The transmembrane region of the TCRalpha chain is highly conserved and to gain insight into the structural and functional role of these residues, single amino acid substitutions were introduced and surface expression and signaling ability studied in T hybridoma cells. Introduction of acid residues within the TCRalpha chain transmembrane region were mostly tolerated, indicating that the net charge within this region of the TCR complex is not crucial to either assembly or signaling. However, mutations of leucine 112 or phenylalanine 127 to aspartic acids (L112D or F127D, respectively) resulted in dramatic loss of surface expression and, therefore, their signaling ability. Intracellular flow cytometry showed that the mutant TCRalpha polypeptides were present at levels comparable to wild-type, indicating that the reduced surface expression was not a consequence of impaired protein survival. The defect was characterized by immunoprecipitation and showed that residues L112 and F127 were involved in early interactions with the CD3 complex. A large proportion of the TCRalpha chain mutants L112D and F127D consisted of immature protein, indicative of a problem during early assembly of the TCR. Our findings provide evidence for the involvement of the conserved L112 and F127 residues of the TCRalpha chain transmembrane region in the assembly process of the TCR complex.


Comparison of ability of time-domain and spectral-domain optical coherence tomography to detect diffuse retinal nerve fiber layer atrophy.
Our aim was to evaluate and compare diagnostic capabilities of time-domain (Stratus) and spectral-domain (Cirrus) optical coherence tomography (OCT) to detect diffuse retinal nerve fiber layer (RNFL) atrophy. This study assessed 101 eyes from 101 glaucoma patients with diffuse RNFL atrophy and 101 eyes from 101 age-matched healthy individuals. Two experienced glaucoma specialists graded red-free RNFL photographs of eyes with diffuse RNFL atrophy using a four-level grading system. The area under the receiver operating characteristic curves (AUC) of normal eyes was compared with that of eyes with diffuse atrophy. Sensitivity and specificity of each OCT device were calculated on the basis of its internal normative database. The largest AUC for Stratus and Cirrus were obtained for average RNFL thicknesses (0.96 and 0.94, respectively). Comparison of the AUC with different RNFL atrophy grades revealed no significant difference between the two OCT devices. Using an internal normative database at a <5 % level, the overall sensitivity of Stratus ranged from 58.0 to 84.0 %, whereas that of Cirrus ranged from 75.0 to 87.0 %. According to the normative database, the highest Stratus sensitivity was obtained with the temporal-superior-nasal-inferior-temporal (TSNIT) thickness graph, and the highest Cirrus sensitivity with the TSNIT thickness graph and the deviation map. The AUC obtained from Cirrus were comparable with those from Stratus. On the basis of their normative databases, these devices had similar diagnostic accuracy. Our results suggest that the diagnostic capabilities of the two instruments to detect diffuse RNFL atrophy are similar.


The effect of proxicromil, a new oral chromone derivative, in antigen challenge tests is asthmatic patients.
Proxicromil is a compound shown in biological tests to have anti-allergic properties. It is well absorbed in humans after oral administration. In order to assess its anti-allergic activity in humans, experiments were carried out in asthmatic patients to investigate its inhibitory effects upon the bronchoconstrictor response to antigen challenge. Two controlled experiments were carried out according to randomized double blind crossover designs, in each of which ten selected patients were pretreated orally with proxicromil before being challenged with inhaled doses of antigen. Inhibition of the immediate response to antigen challenge by single and repeated doses was meaured by intermittent recordings of forced expiratory volume in one second (FEV1) for 30 minutes after challenge. The duration of action of proxicromil and studied by varying the time between administration of the last dose given and inhalation of the antigen. The results showed that proxicromil significantly protected patients against the immediate response to challenge, and possessed a long duration of action of at least 12 hours.


Glomerular basement membrane thickness in normal adults and its application to the diagnosis of thin basement membrane disease: an Indian study.
Microscopic hematuria of non-urologic origin warrants ultrastructural study of renal biopsy. Thinning and variations in the texture of glomerular basement membrane (GBM) are difficult to be recognized under light microscope; transmission electron microscope (TEM) therefore plays a vital role in identifying such changes. Ultrastructural morphometry is a valuable diagnostic aid when GBM is suspected of being abnormally thin. In an effort to determine the normal GBM thickness (GBMT) in Indian adults and to determine the cutoff value of GBMT for a diagnosis of thin basement membrane disease (TBMD), we determined GBM thickness in 25 normal adults. Postmortem biopsies of 25 normal adults (16 males and 9 females) aging between 18-58 years were included in the study. GBM thickness was determined through ultrastructural morphometry on accurately enlarged electron micrographs as harmonic mean of 50 orthogonal intercepts across the GBM in each case. Study revealed a mean GBM thickness of 321 nm with a standard deviation (SD) of 28 nm. Mean-2SD (321-56), that is 265 nm, was fixed as cutoff value of GBMT for the diagnosis of TBMD. A systematic split study of control subjects revealed thicker GBM (329+/-38 nm) in higher age group (35-60 years) as compared to GBMT (316+/-21 nm) in lower age group (18-30 years). Males in higher age group also revealed thicker GBM (males: 343+/-39 nm versus females: 300+/-12 nm). Ten patients with non-urologic hematuria and having GBMT<265 nm were diagnosed as cases of TBMD. Patients with TBMD revealed significantly attenuated GBM as compared to age and sex matched controls (214 +/- 40 nm versus 311 +/- 17 nm; p<0.0005). No overlap was observed in the distribution of GBMT in patients of TBMD and age and sex matched controls. Ultrastructural morphometry is the ultimate and appropriate method for diagnosing TBMD.


Promotion of skeletal muscle differentiation by K252a with tyrosine phosphorylation of focal adhesion: a possible involvement of small GTPase Rho.
K252a, a protein kinase inhibitor, acts as a neurotrophic factor in several neuronal cells. In this study we show that K252a enhanced the differentiation of C2C12 myoblasts as well as tyrosine phosphorylation of several focal adhesion-associated proteins including p130(Cas), focal adhesion kinase, and paxillin. The tyrosine phosphorylation of these proteins, reaching a maximum at 30 min after K252a treatment, closely correlated with the colocalization of these proteins in focal adhesion complexes and the coimmunoprecipitation of these proteins with p130(Cas). In addition, K252a stimulated longitudinal development of stress fiber-like structures and cell-matrix interaction in postmitotic myoblasts and eventually formation of well-developed myofibrils in multinucleated myotubes. Herbimycin A, a potent inhibitor of Src family kinases, and cytochalasin D, a selective disrupting-agent of actin filament, completely inhibited K252a-induced tyrosine phosphorylation as well as myoblast differentiation. Similar inhibitory effect was observed in the cells scrape loaded with a Rho inhibitor, C3 transferase, and the treatment of K252a induced a rapid translocation of Rho. These results are consistent with the model that Rho-dependent tyrosine phosphorylation of focal adhesion-associated proteins plays an important role in skeletal muscle differentiation.


Thermomechanical manipulation of aromatic peptide nanotubes.
Self-assembling aromatic dipeptides are among the smallest known biological materials which readily form ordered nanostructures. The simplicity of nanotube formation makes them highly desirable for a range of bionanotechnology applications. Here, we investigate the application of the atomic force microscope as a thermomechanical lithographic tool for the machining of nanotubes formed by two self-assembling aromatic peptides; diphenylalanine and dinapthylalanine. Trenches and indentations of varying depth and width were patterned into the peptide tubes with nanometer precision highlighting the ability to thermally machine and manipulate these robust and versatile nanotubes.


Cell cycle regulatory protein 5 (Cdk5) is a novel downstream target of ERK in carboplatin induced death of breast cancer cells.
Neuronal cell specific cyclin-dependent kinase 5 (Cdk5) is a known regulator of neurodegenerative disorders such as Alzheimer's and Parkinson's diseases. We report that Cdk5 also plays an important role in the proliferation of breast cancer cells MCF-7 and MDA MB-231 and is functionally involved in chemosensitivity as well as in cell death pathways induced by anti-cancer drug carboplatin (Carb). Here, we demonstrate that carboplatin induced Cdk5 activation under positive regulation of ERK, promotes cell death in MCF-7 and MDA MB-231 cells. DNA-damage stress enhanced ERK activity utilizes Cdk5 as one of its downstream targets for the execution of death signal in carboplatin induced death in MCF-7 and MDA MB-231 cells. Additionally, present data clearly indicates that activated Cdk5 modulates p53 transactivation in MCF-7 cells. However, in p53 mutant MDA MB-231 cells, Cdk5 mediated cell death is likely to be p53 independent. Collectively, our findings not only draw attention to the extra-neuronal functions of Cdk5 but also propose Cdk5 as a novel and potential therapeutic target of chemotherapeutic drugs.


Optimal non-invasive imaging test selection for the diagnosis of ischaemic heart disease.
The prevalence of angina is high in the general population, and increases with age in both sexes. Little consensus exists about which test is preferable when one is required for diagnosis, including significant differences in the current US and European guidelines. However, the recent PROMISE and SCOT-HEART trials incorporating the use of CCTA have demonstrated that an anatomical strategy is a reasonable alternative initial approach to use in intermediate-risk patients with stable chest for the diagnosis of IHD. Contemporary approaches should therefore consider both functional and anatomical strategies in an integrated decision-making model.


Diagnostic significance of urinary growth hormone measurements in children with growth failure: correlation between serum and urine growth hormone.
Twelve-h overnight urine and serum samples obtained simultaneously at 20-min intervals were assayed for growth hormone (GH). Ninety-one children, 5 to 16 y (Tanner stage 1 to 3) participated; group 1 were healthy children, group 2 were children with organic GH deficiency, and group 3 had idiopathic growth failure and normal GH stimulation tests. Serum pool GH concentrations in group 1 were similar to those in group 3 (3.3 +/- 0.3 versus 3.4 +/- 0.2 micrograms/L); group 2 had significantly lower GH concentrations (1.6 +/- 0.2 micrograms/L). Plasma IGF-I levels were significantly greater in groups 1 (14.2 +/- 2.6 nmol/L, p less than 0.001) than in groups 2 and 3 (2.6 +/- 0.5 and 5.5 +/- 0.7 nmol/L, respectively). Urinary GH (mean +/- SEM) standardized for body weight (micrograms/kg) in group 1 (0.31 +/- 0.02) was significantly greater than in group 2 (0.14 +/- 0.01) and group 3 (0.20 +/- 0.01). However, when expressed as microgram/mol creatinine, the output of GH was similar in group 1 (4.0 +/- 0.3) and group 3 (3.4 +/- 0.3); both groups had significantly greater output compared to group 2 (1.3 +/- 0.2). Urinary IGF-I (nmol/kg) in group 1 (0.22 +/- 0.02) was significantly greater than in group 2 (0.12 +/- 0.01) or group 3 (0.07 +/- 0.01). Urinary GH correlated with serum pool GH concentration (r = 0.64, p less than 0.001). Although urinary GH output reflects endogenous GH secretion, the overlap between groups 1 and 3 precludes using urinary GH measurements as a diagnostic test for GH deficiency in children with idiopathic growth failure.


Predictive validity of specialty choice data from AAMC graduation questionnaire. Association of Medical Colleges.
Several previous studies have used data from the Association of American Medical Colleges' annual graduation survey to address questions about medical students' specialty preferences. Only recently, however, has it become possible to test the validity of these data as indicators of the specialties in which students will actually receive training. Comparisons of 1983 graduation questionnaire data with data on the third-year residencies for the same cohort reveal that the specialty preferences indicated on the questionnaire were good predictors of the residency programs the respondents were in during the third year following graduation.


Nephrolithiasis in a child with glucose-galactose malabsorption.
Glucose-galactose malabsorption (GGM) is a rare autosomal recessive disorder of intestinal transport of glucose and galactose, leading to watery diarrhea, dehydration, failure to thrive, or early death. We report a female newborn with GGM, whose clinical diagnosis was confirmed by mutational analysis of the SGTL1 gene. Bilateral nephrolithiasis was discovered after an episode of hematuria. Metabolic causes of nephrolithiasis were not found. The most likely explanation for the development of nephrolithiasis is chronic diarrhea leading to dehydration and highly concentrated urine. High fluid intake and rigorous prevention of dehydration is therefore advised for these patients. Furthermore, life-long monitoring of their renal status, including regular ultrasound examinations, is warranted.


Comparisons of the structural proteins of avian infectious bronchitis virus as determined by western blot analysis.
The antigenic diversity of ten strains of avian infectious bronchitis virus (IBV) was examined by Western blot analyses using polyclonal antisera specific for the Massachusetts 41 (M41), Gray, Arkansas DPI (Ark DPI), Connecticut (Conn) and Australian T (Aust T) serotypes. Although antigenic variation was found in all three structural viral proteins, the matrix protein appeared to be antigenically the most highly variable. Four distinct antigenic groups, which did not correspond to virulence or pathotype, could be defined according to the variations observed in the matrix protein. Somewhat less variation was seen in the spike polypeptide. The only variation in the nucleocapsid protein was indicated by the lack of a detectable reaction between the Aust T antiserum and the Ark DPI nucleocapsid protein. Antisera made against M41 had the broadest reactivity while antisera against Aust T, the only strain tested which was exotic to the U.S.A., had the greatest specificity.


Expression profiles of NOS isoforms in gingiva of nNOS knockout mice.
Nitric oxide is a gaseous molecule associated with many distinct physiological functions, and is derived from L-arginine catalyzed by nitric oxide synthase (NOS). Nitric oxide synthase has 3 isoforms: nNOS, iNOS and eNOS. Although these NOS isoforms are believed to play an important role in gingival tissue, little information is available on their morphological dynamics. The aim of this study was to investigate the profiles of NOS isoforms in deficiency of nNOS in gingiva of mice. Twelve male (6 normal (C57BL/6) and 6 nNOS knockout) mice were used. All mice were 5-week-old, weighing approximately 20-25 g each. After sacrifice, the jaws of the mice were removed by mechanical means and specimens analyzed by histology, in situ hybridization and immunohistochemistry. Immunohistochemical observation revealed positive staining for iNOS and eNOS, especially in lamina propria. Similar results in the mRNA expression levels were shown by in situ hybridization analysis. It may suggest that iNOS and eNOS compensated nNOS deficiency in the gingiva of nNOS knockout mice.


Isolation and chromosomal localization of GPR31, a human gene encoding a putative G protein-coupled receptor.
The screening of a human genomic library with a chemokine receptor-like probe allowed us to obtain a putative member of the G protein-coupled receptor gene (GPCR) family, designated GPR31. Its deduced amino acid sequence encodes a polypeptide of 319 amino acids that shares 25-33% homology with members of the chemokine, purino, and somatostatin receptor gene families. Amino acid sequence comparison reveals that the best match in the protein databases is with the human orphan GPCR called HM74 (33% identity). Southern genomic analysis of the GPR31 gene shows a hybridization pattern consistent with that of a single-copy gene. Using fluorescence in situ hybridization, we have determined the chromosomal and regional localization of the GPR31 gene at 6q27. The GPR31 mRNA is expressed at low levels by several human cell lines of different cellular origins. The phylogenetic analysis suggests that the GPR31 receptor may represent a member of a new GPCR subfamily.


Flavopiridol-induced apoptosis is mediated through up-regulation of E2F1 and repression of Mcl-1.
Flavopiridol treatment can lead to apoptosis via a mechanism that has been associated with down-regulation of Mcl-1. Likewise, recent studies from our laboratory demonstrated that E2F1 leads to transcriptional repression of Mcl-1 and subsequently apoptosis. Given the ability of cyclin/cyclin-dependent kinase 2 antagonists to kill transformed cells, we surmised that flavopiridol may stabilize E2F1 and enhance apoptosis via repression of Mcl-1. Here we demonstrate that flavopiridol is associated with a dose-dependent increase in E2F1 protein levels, a corresponding reduction in Mcl-1, and apoptosis in H1299 lung carcinoma cells. Treatment of H1299 cells with 200 nM flavopiridol resulted in the rapid elevation of E2F1 and reduction in Mcl-1 levels within 12 h of treatment. The elevation of E2F1 and reduction in Mcl-1 clearly preceded the induction of apoptosis. Both H1299 and NIH3T3 fibroblast cell lines that constitutively express Mcl-1 under the control of the cytomegalovirus promoter have no reductions in Mcl-1 levels with flavopiridol treatment and are resistant to apoptosis induced by flavopiridol. H1299 cells that have E2F1 deleted through RNAi vector targeting are less sensitive to flavopiridol-induced cell death, and likewise, mouse embryo fibroblast cell lines deficient in E2F1 are less susceptible to apoptosis induced by flavopiridol compared with wild-type control fibroblasts. These data suggest that apoptosis induced by flavopiridol is dependent on the enhancement of E2F1 levels and the repression of Mcl-1.


[Return to Work between the Conflicting Priorities of Work and Health Orientation].
The basic aim of this study was to analyse health-related exit processes from working life and their conditional constellations. It focused on biographical coping in the context of professional reorientation and Return to Work (RTW). The aim was to describe, among other things, phases, characteristics and mechanisms of coping with a double-folded biographical disruption, i. e. coping with the chronic disease and the vulnerable occupational situation. The study focused on 6 women and 4 men between 25 and 57 years of age who were interviewed (episodically-narrative) at 2 different points in the survey period from 2011 to 2014: during their medical respectively vocational rehabilitation (t1) and again about one year later (t2). The overall characteristic of all cases was the initiated or already faced health-related occupational biographical disruption caused by a chronic musculoskeletal disease partly accompanied by psychosomatic issues or triggered by a mental illness. This study followed the methodological approach and research style of the Grounded Theory 1. A health-related exit from working life is usually gradual and is caused by complex risk constellations. Only in the interplay of personal and contextual factors does a framework for the double-folded biographical disruption develop. The resulting social, biographical and health challenges lie in the areas of private and working life. RTW is experienced as an experimental phase to return to everyday working life under limited health conditions. A key finding of this study is the recognition that the transformation of the importance of health is taking place in exit and reorientation processes. This paper focuses on its significance for the rehabilitation and RTW process. The applied perspective on biographical processes makes it possible to describe health-related breaks as a change in status from healthy to sick, from high performance to limited performance. Professional stakeholders in medical and rehabilitative settings should be made more aware of the identity-building processes, individual professional biographical crises and disease management processes of those affected. It is important not only to evaluate RTW as the one and only success, key outcome and end of the rehabilitation process, but to understand RTW as a continuing process of occupational reorientation under limited health conditions and to design it as a participatory process.