Direct anti-inflammatory effects of granulocyte colony-stimulating factor (G-CSF) on activation and functional properties of human T cell subpopulations in vitro.
We investigated the direct effects of human granulocyte colony-stimulating factor (G-CSF) on functionality of human T-cell subsets. CD3+ T-lymphocytes were isolated from blood of healthy donors by positive magnetic separation. T cell activation with particles conjugated with antibodies (Abs) to human CD3, CD28 and CD2 molecules increased the proportion of cells expressing G-CSF receptor (G-CSFR, CD114) in all T cell subpopulations studied (CD45RA+/CD197+ naive T cells, CD45RA-/CD197+ central memory T cells, CD45RA-/CD197- effector memory T cells and CD45RA+/CD197- terminally differentiated effector T cells). Upon T-cell activation in vitro, G-CSF (10.0 ng/ml) significantly and specifically enhanced the proportion of CD114+ T cells in central memory CD4+ T cell compartment. A dilution series of G-CSF (range, 0.1-10.0 ng/ml) was tested, with no effect on the expression of CD25 (interleukin-2 receptor α-chain) on activated T cells. Meanwhile, G-CSF treatment enhanced the proportion of CD38+ T cells in CD4+ naïve T cell, effector memory T cell and terminally differentiated effector T cell subsets, as well as in CD4- central memory T cells and terminally differentiated effector T cells. G-CSF did not affect IL-2 production by T cells; relatively low concentrations of G-CSF down-regulated INF-γ production, while high concentrations of this cytokine up-regulated IL-4 production in activated T cells. The data obtained suggests that G-CSF could play a significant role both in preventing the development of excessive and potentially damaging inflammatory reactivity, and in constraining the expansion of potentially cytodestructive T cells.


Interictal sharp EEG transients in neonatal seizures.
This study describes the differences between several quantifiable variables that characterize interictal sharp EEG transients (SETS) recorded from neurologically ill neonates with proven electrographic seizures and a comparison group of apparently neurologically well babies with no known seizures. The abundance (number of sharp EEG transients per ten minutes), waveform morphology, repetitive behavior, and spatial distribution of SETS provide interpretive guidelines that help discriminate between these two patient populations.


The in vitro effects of metal cations on eukaryotic cell metabolism.
The in vitro cytotoxicity of nine metal cations common in dental casting alloys was evaluated using Balb/c 3T3 fibroblasts and four toxicity parameters: total protein production, 3H-leucine incorporation, 3H-thymidine incorporation, and MTT-formazan production. Concentrations causing 50% toxicity compared to controls (TC50's) and reversibility of these effects were determined. The range of potency of the metal cations was 2-3 orders of magnitude, with Cd2+ showing the greatest potency and In3+ showing the least. Potency did not correlate with atomic weight for these metals. For each metal cation, the TC50's of the various toxicity parameters were similar in most cases. However, several cations (Cu2+, Ga3+) showed greater potency with 3H-thymidine incorporation. Reversibility of the toxic effects was observed for all cations; the effects generally became irreversible at concentrations in the range of the TC50 value for each cation. Several stimulatory effects were seen. Small but statistically significant stimulations were observed after 24 h of metal exposure for Ag1+, Au4+, Cu2+, Ga3+, and Ni2+. Residual stimulations 24 h after removal of the metal cations were observed for Au4+, Cd2+, Ni2+, and Zn2+. Stimulations always occurred at concentrations below the TC50 concentrations. This study should be useful in evaluating the potential cytotoxic effects of metal cations released from dental alloys.


The Xenopus noggin promoter drives roof-plate specific transcription.
During vertebrate neural development, inductive signals derived from the roof plate specify dorsal neural cell types of spinal cord as well as adjacent dermomytotome. Noggin has been demonstrated to play a pivotal role in this signaling network but how its expression is regulated remains unclear. To investigate this issue, we identified a 2066 bp Xenopus noggin 5' flanking sequence which recapitulates the roof-plate expression of endogenous gene in transgenic frog tadpoles and we further mapped the roof-plate enhancer to a sequence as short as 79 bp. Our results, therefore, not only shed light on but also provide a powerful tool to the study of neural and somite patterning.


Biotransformation of polycyclic aromatic compounds by fungi.
Incubations of several polycyclic aromatic hydrocarbons (PAHs) and heteroaromatic compounds with a series of common micro-organisms have been performed. The PAHs were not metabolized by any of the fungi studied. The sulphur-containing heterocyclic aromatic compounds dibenzothiophene, thioxanthone and thiochromanone were oxidized at sulphur by C. elegans. Other fungi are capable of oxidation at the sulphur atom of dibenzothiophene and thioxanthone. C-1 and C-3 methyl substituted thioxanthones are hydroxylated at the methyl group by C. elegans.


Protonophoric activity of fatty acid analogs and derivatives in the inner mitochondrial membrane: a further argument for the fatty acid cycling model.
The protonophoric (uncoupling) action of various long-chain fatty acids and their derivatives in mitochondria was investigated as related to their ability for rapid transbilayer movement in the inner mitochondrial membrane (flip-flop) and interaction with the ADP/ATP carrier (AAC). Flip-flop was assessed from a rapid decrease of internal mitochondrial pH. It was found that long-chain unsubstituted fatty acids (with the exception of very-long-chain unbranched homologs) and their thia and oxa analogs performed a rapid flip-flop, inhibited AAC activity and increased proton permeability of the inner mitochondrial membrane, resulting in dissipation of mitochondrial membrane potential and increased resting state respiration. Bipolar fatty acid analogs, i.e., those containing a second carboxylic group or OH group(s) at the hydrocarbon tail, phenyl-substituted fatty acid derivatives, and fatty acid analogs containing strongly ionized sulfonyl or sulfate groups instead of the carboxylic group, did not flip-flop and were not uncoupling, although some of them were weak inhibitors of AAC. These results provide further confirmation of the fatty acid cycling model (V. P. Skulachev, FEBS Lett. 294, 158-162, 1991) in which the protonophoric function of fatty acids is a result of the spontaneous transbilayer passage of undissociated (protonated) molecules of the fatty acid from the external side of the inner mitochondrial membrane to the matrix side and the AAC-mediated transport of the fatty acid anion in the opposite direction.


Complete sequence and in vitro expression of a tissue-specific phosphatidylinositol-linked N-CAM isoform from skeletal muscle.
Neural cell adhesion molecules (N-CAMs) are a family of cell surface sialoglycoproteins encoded by a single copy gene. A full-length cDNA clone that encodes a nontransmembrane phosphatidylinositol (PI) linked N-CAM of Mr 125 x 10(3) has been isolated from a human skeletal muscle cDNA library. The deduced protein sequence encodes a polypeptide of 761 amino acids and is highly homologous to the N-CAM isoform in brain of Mr 120 x 10(3). The size difference between the 125 x 10(3). The size difference between the 125 x 10(3) Mr skeletal muscle form and the 120 x 10(3) Mr N-CAM form from brain is accounted for by the insertion of a block of 37 amino acids called MSD1, in the extracellular domain of the muscle form. Transient expression of the human cDNA in COS cells results in cell surface N-CAM expression via a putative covalent attachment to PI-containing phospholipid. Linked in vitro transcription and translation experiments followed by immunoprecipitation with anti-N-CAM antibodies demonstrate that the full-length clone of 761 amino acid coding potential produces a core polypeptide of Mr 110 x 10(3) which is processed by microsomal membranes to yield a 122 x 10(3) Mr species. Taken together, these results demonstrate that the cloned cDNA sequence encodes a lipid-linked, PI-specific phospholipase C releasable surface isoform of N-CAM with core glycopeptide molecular weight corresponding to the authentic muscle 125 x 10(3) Mr N-CAM isoform. This is the first direct correlation of cDNA and deduced protein sequence with a known PI-linked N-CAM isoform from skeletal muscle.


Captopril lacks the antidepressant-like activity in animal models.
Captopril, an angiotensin converting enzyme inhibitor, was evaluated for a potential antidepressive activity in several animal models. The drug administered in doses of 3-30 mg/kg ip neither affected the reserpine- or apomorphine-induced hypothermia in mice nor reduced the immobility time in the forces swimming test in mice and rats. Moreover, captopril administered repeatedly (10 mg/kg ip, twice daily for 14 days) neither changed the density or affinity of cortical beta-adrenoceptors nor modified the nomifensine-induced locomotor hyperactivity in rats. These results suggest that captopril has no antidepressant-like activity in animal models.


Clinical significance of umbilicoportal manometry.
Ninety-six adult patients had measurements of portal pressur over 1 to 5 days via indwelling extraperitoneal umbilicoportal catheters. Liver biopsy specimens obtained during catheterization showed 50 patients to have a normal liver; the remainder had liver disease. Portal pressure averaged 16.08 +/- 2.87 (SED) cm of saline in normal patients. Ten patients, 6 with cirrhotic and 4 with normal livers, were recatheterized 1.5 days to 7 months later when they came to laparotomy. In all but one, portal pressures were decreased during anesthesia and laparotomy. Twenty additional patients undergoing cholecystectomy had portal pressures measured before and after laparotomy, and after recovery from anesthesia for 1 to 3 postoperative days. Laparotomy caused a decrease in portal pressure of 2.7 +/- 1.3 (SED) cm of saline; after recovery from anesthesia portal pressure was higher by 2.5 +/- 1.7 (SED) cm of saline. Umbilicoportal catheterization is a safe and accurate technique for studying the portal system. In the intact unanesthetized state, we consider 22 cm of saline to be the upper limit of normal for portal pressure.


[Pulsed high-dose dexamethasone in resistant immune thrombocytopenic purpura].
Most patients with chronic idiopathic thrombocytopenic purpura (TTP) show a good initial response to treatment with corticosteroids. However the disease relapses in more than 90% when steroid dosage is reduced. Recently 100% success was reported for a new therapeutic protocol in 12 patients (ranging in age from 13-60, half of them women) with chronic ITP refractory to corticosteroids or to splenectomy. They were given pulsed therapy with oral dexamethasone, 40 mg/day on 4 consecutive days each month, for 6 months. This treatment protocol was used in an attempt to avoid splenectomy. 5 patients (42%) had a complete response but 7 did not. The median follow-up in those who responded was 7 months (range 6-8). Of the 7 who did not respond, 5 had not completed treatment: 3 because of urgent splenectomy and 2 because of lack of response after 3 courses of therapy accompanied by side-effects. Most patients suffered typical corticosteroid side-effects, principally restlessness, insomnia, and withdrawal effects. These were milder and better tolerated in those treated with Dexacort solution (20 mg ampules) rather than dexamethasone tablets. Despite complete response in only 5 of the 12 patients (42%), we feel that pulsed high-dose dexamethasone is effective and should be tried in TTP refractory to conventional corticosteroid therapy, before resorting to splenectomy.


A finger sweat chloride test for the detection of a high-risk group of chronic pancreatitis.
Mutations of the cystic fibrosis transmembrane conductance regulator (CFTR) gene are associated with chronic pancreatitis in Caucasians. We developed a simple method for measuring finger sweat chloride concentration to test whether CFTR dysfunction underlies chronic pancreatitis in Japan where cystic fibrosis (CF) is rare. We studied 25 patients with chronic (21 alcoholic and 4 idiopathic) pancreatitis and 25 healthy volunteers. Sweat chloride concentrations were measured by a finger sweat chloride test. We analyzed DNA for 20 common CFTR mutations in Europeans, 9 CF-causing mutations in Japanese, and 2 polymorphic loci, a poly-T tract and (TG) repeats, at intron 8. Thirteen patients (52%) had sweat chloride levels >60 mmol/L, a level consistent with CF, while only 4 (16%) healthy subjects exceeded this level. The 29 CF mutations and the 5T allele were detected in neither the patients nor controls. The (TG) 12 allele was common in both the patients (58%) and controls (48%). The (TG) 12/12 genotype was common in alcoholic pancreatitis (29%) compared with the (TG) 11/11 (10%). Patients with the (TG) 12/12 genotype had significantly higher sweat chloride concentrations than the controls. CFTR dysfunction as evidenced by a finger sweat chloride test is present in about half of Japanese patients with chronic pancreatitis, suggesting that this test may be useful for detecting the high-risk group. A higher proportion of the (TG) 12 allele may be a genetic background for elevated sweat chloride concentrations in Japanese patients.


Interdigitating reticulum cell tumor of lymph node: a case report and literature review.
Interdigitating reticulum cell (IRC) tumor is a rare tumor arising from the antigen-presenting cell - interdigitating reticulum cell. A 41-year-old male presented with lumps in the left neck and bone pain. Further investigations revealed multiple left neck and para-aortic lymphadenopathy, and multiple bony lesions. Histological examination of the lymph node showed proliferation of unusual, large, round neoplastic cells mimicking large cell lymphoma. Immunophenotypic and ultrastructural studies confirmed this tumor to be arising from an interdigitating reticulum cell. A review of reported IRC tumors illustrates the variability of this tumor in clinical and pathological features, which differ from other dendritic reticulum cell tumors.


Production and availability of thromboplastin in endothelial cells: the effects of thrombin, endotoxin and platelets.
Freshly prepared endothelial cells from umbilical cord veins were demonstrated to possess a weak but significant thromboplastin activity. Upon exposure of cultured endothelial cells to catalytically active thrombin (4.5 U/ml) or endotoxin (0.05 microgram/ml), the thromboplastin activity of the cells was increased 10-40-fold during 5 h incubation, and with the additional presence of washed, isolated platelets during the incubation, the activity was enchanced up to 170-fold. Platelets or catalytically inactivated thrombin added alone were largely ineffective as stimulants. 75-80% of the enhanced thromboplastin activity became available on the surface of the cultured cells as demonstrated by utilizing thromboplastin antibodies. Such exposed activity is suggested to be important in thrombotic situations where initial formation of thrombin may significantly accelerate the generation of thrombin by a positive feedback effect upon thromboplastin synthesis in the endothelial cells.


Rare presentation of osteoarticular tuberculosis.
The varied clinical presentation of osteoarticular tuberculosis makes the diagnosis an enigma. This report underlines the fact that osteoarticular tuberculosis can present in the most atypical pattern. It also emphasises the need for a high index of clinical suspicion and the low threshold for tissue biopsy for establishing the diagnosis.


Validating a simple scoring system to predict malignancy and invasiveness of intraductal papillary mucinous neoplasms of the pancreas.
The objective of the present study was to identify reliable preoperative factors predicting malignancy or invasiveness of intraductal papillary mucinous neoplasm (IPMN) of the pancreas and the effectiveness of a diagnostic scoring system based on these factors. Between August 1994 and December 2007, 204 patients underwent pancreatic resection for IPMN at a single institute. Medical records were reviewed retrospectively, and a new diagnostic scoring system for predicting malignant IPMN preoperatively was designed. Univariate analysis revealed nine significant predictors of both malignant and invasive IPMN: age > or =60 years, history of pancreatitis, presence of mural nodule(s), diameter of main pancreatic duct (MPD) >6 mm, main duct or mixed type, total bilirubin >1.2 mg/dl, CA-19-9 >37 U/ml, tumor location in the pancreatic head, and tumor size >30 mm. Multivariate analysis showed that age, pancreatitis, mural nodule(s), and MPD diameter were independent predictors of invasive IPMN, and that all these parameters, plus elevated carbohydrate antigen-19-9 (CA-19-9), were independent predictors of malignant IPMN. A scoring system based on these five factors, each assigned 1 point, and with a cut-off of 3 points, could predict malignant IPMN with a sensitivity of 50.7% and a specificity of 90.1%. The 5-year survival rates of patients with benign and malignant IPMN were 95.0% and 64.0%, respectively. Our scoring system using five independent factors (age > or =60 years, history of pancreatitis, presence of mural nodule(s), elevated level of CA-19-9, and MPD diameter >6 mm) may be helpful for predicting malignancy and postoperative survival.


Analysis of hypoxia-inducible factor 1alpha expression and its effects on invasion and metastasis.
Hypoxia-inducible factor 1 (HIF-1) plays an important role in human cancer cell invasion and metastasis. As a result, overexpression of the HIF-1alpha subunit in biopsy specimens is associated with increased patient mortality in several common cancers, including breast adenocarcinoma and oropharyngeal squamous cell carcinoma. Here, we describe methods for immunohistochemical detection of HIF-1alpha in tumor biopsy sections and ex vivo assays for analyzing the effects of hypoxia and HIF-1 on cancer cell invasiveness and cell-cell adhesion.


A Systematic Review of Services to DHH Children in Rural and Remote Regions.
Children in regional, rural and remote areas have less access to services than those living in urban areas. Practitioners serving children with a hearing loss have attempted to address this gap, however there are few studies investigating service access and experiences of non-metropolitan families and professionals. This systematic review evaluates the literature on service provision to children with a hearing loss living in regional, rural and remote areas of Australia. A search of five databases, the gray literature and a prominent author located 37 relevant documents. The journal articles were rated for quality and the findings of all documents were themed. The evidence from this review indicates that children with a hearing loss living in regional, rural and remote Australia experience reduced quality and frequency of service. Further investigation is needed to identify the accessibility and suitability of services for children with a hearing loss in non-metropolitan areas.


[Histofluorescence and histochemical analysis of adrenergic and cholinergic innervation of the lungs in burns].
Neurohistochemical methods were applied to study adrenergic and cholinergic nervous structures of pulmonary tissue in 30 patients aged 14-82 who had died of burn disease at various stages of its progress (shock, toxemia, septic toxemia). Autopsies performed within 4 hours after the patients' death evidenced mediators depletion in perivascular and peribronchial plexuses as well as intensive luminescence of nervous fibers considered as compensatory adaptation. There was cholinesterase hypoactivity in cholinergic plexuses. It is established that the failure of adaptive-trophic sympathetic regulation of pulmonary tissues including relevant vessels and bronchi results in diminution of pulmonary compensatory and adaptive potential. This should be allowed for in the treatment of burn disease complications.


Safe Zone for the Plantar Portal: A Cadaveric Study.
Understanding the plantar nerve anatomy is crucial for safe endoscopic surgery of the sole. We aimed to anatomically dissect the lateral aspect and soles of cadaveric feet to investigate the safety of peroneus longus tendoscopy with a plantar lateral portal and the safe zones for plantar portals. We studied 36 feet of 24 cadavers (mean age, 86.5 years). A cannula for 2.7-mm scope was inserted from the plantar lateral portal to the peroneus longus tendon, and the positional relationship between the cannula and sural nerve was observed. Then, the soft tissue of the sole was dissected, and the relationships between the plantar nerve and flexor digitorum longus tendon and flexor hallucis longus tendon was observed. The plantar nerve course was digitally imaged and uploaded into Image J software to determine nerve position. We further observed the positional relationship between the cannula and plantar nerve. The mean minimum distance between the cannula and sural nerve was 13.8 mm, and the closest distance was 4.2 mm, allowing for the relatively safe creation of a plantar lateral portal. The use of the plantar lateral portal and evaluation of the peroneal tendon was safe with respect to the lateral plantar nerve as the nerve was in a different tissue layer of the foot. Dissection of the plantar foot demonstrated a relatively safe zone, 36.4% to 56% along a line between the medial aspect of the base of the first metatarsal bone to the proximal tip of the fifth metatarsal. This region may allow for a plantar endoscopic portal; however an anatomic variation may result in the plantar nerve being within this zone. The flexor digitorum longus tendon and peroneus longus tendon passed through the deep layer of the relatively safe zone. Peroneus longus tendoscopy was relatively safe to perform from a plantar lateral portal. No neurovascular structure exists on the slightly medial aspect of the central region of the sole, potentially allowing for a relatively safe creation of plantar central portal. An approach from the plantar central portal to the flexor digitorum longus tendon, flexor hallucis longus tendon, and peroneus longus tendon allows for a greater range of vision and treatment options as compared with conventional approaches. The combination of the plantar central portal with portals such as the plantar lateral portal may further the development of endoscopic surgery of the sole. We found the anatomic characteristics of a relatively safe zone for the plantar portal for plantar lateral portal.


Randomised clinical trial: efficacy of peginterferon alfa-2a in HBeAg positive chronic hepatitis B patients with lamivudine resistance.
Previous studies suggested that a finite course of peginterferon alfa-2a may offer an alternative rescue therapy for patients with lamivudine resistance. However, because of the limitation of study design and small sample size, it is difficult to make definitive conclusion. To explore the role of peginterferon alfa-2a, in the rescue treatment of HBeAg-positive chronic hepatitis B patients with lamivudine resistance. In this randomised study, chronic hepatitis B patients with lamivudine resistance were treated with peginterferon alfa-2a for 48 weeks (n=155) or adefovir for 72 weeks (n=80). All enrolled patients were treated with lamivudine for the first 12weeks. At 6 months posttreatment, 14.6% (18/123) of peginterferon alfa-2a-treated patients achieved HBeAg seroconversion, in contrast to 3.8% (3/80) of adefovir-treated patients after 72 weeks continuous therapy (P=0.01). For peginterferon alfa-2a-treated patients, the rate of HBeAg seroconversion at week 72 was significantly higher in patients who had HBsAg decline >0.5 Log(10) IU/mL from baseline at week 24, compared with patients with HBsAg decline ≤0.5 Log(10) IU/mL from baseline at week 24 (25.5% vs. 7.7%, P=0.01). After 72 weeks continuous adefovir treatment, 22.5% of patients achieved HBV DNA <80 IU/mL, compared with 10.6% in peginterferon alfa-2a-treated patients at 6months off-treatment (P=0.02). Overall, the response to peginterferon alfa-2a among patients with lamivudine resistance was suboptimal. HBeAg seroconversion rate at week 72 by 48 weeks peginterferon alfa-2a treatment was higher than continuous adefovir therapy. Monitoring HBsAg levels can help to predict response to peginterferon alfa-2a.


Structure and binding properties of serum albumin in uremic patients at different periods of hemodialysis.
Few diagnostic methods are available that describe uremia related changes of the albumin molecule structure in hemodialysis patients. The impaired human serum albumin (HSA) function is an essential part of the uremic syndrome and probably influences the long-term outcome of patients on maintenance dialysis. The albumin binding capacity (characterized for different binding centers on the molecule) is one of the relevant clinical parameters. During the current study, marker substances were utilized to evaluate center-specific binding capacity. Patients were divided into 3 groups depending on the time on hemodialysis (HD) treatment (in years) with healthy blood donors as control. Compared to healthy persons, results demonstrate a considerable impairment of binding characteristics in HD patients. Only in patients on maintenance HD for more than 5 years did ligand binding properties improve significantly. A correlation between the time of chronic HD and the recovery in binding capacity was found for the majority of binding centers of the HSA molecule. Similar results were seen applying such analytical methods as thermography (melting points) and thermofluorescence. Binding capacity impairment found for specified binding centers on the HSA molecule as the main serum carrier protein may have a direct impact on different clinical situations and the HD long-term outcome.


Determinants of myocardial blood flow response to cold pressor testing and pharmacologic vasodilation in healthy humans.
Response of myocardial blood flow (MBF) to sympathetic stimulation with cold is modulated by endothelium-related factors and is typically altered in the presence of coronary risk factors. Determinants of flow response to cold pressor testing (CPT) in normal volunteers at low risk for CAD remain less well defined, especially relative to baseline conditions such as hemodynamics and MBF, plasma substrate and lipid levels, and total pharmacologically stimulated vasodilator capacity. In 50 normal volunteers (42+/-13 years; 31 women) without coronary risk factors, insulin resistance, or family history of diabetes/premature CAD, MBF was measured with (13)N-ammonia and PET at baseline, during CPT, and during pharmacologic hyperemia. Sympathetic stimulation with CPT raised heart rate and blood pressure and thus MBF (Delta MBF=0.23+/-0.09 ml/min/g). MBF response, defined in absolute flow units as the difference between CPT and baseline, was independent of age, gender, heart rate, and blood pressure and rate-pressure product (RPP) at baseline as well as plasma substrate and lipid levels with the exception of an association with HDL cholesterol (rho=0.40, p=0.005) but depended on the change in RPP from rest (rho=0.33, p=0.019). Finally, changes in coronary vascular resistance in response to CPT were associated with changes in pharmacologic vasodilation (rho=0.56, p<0.0001). MBF response to sympathetic stimulation with cold (NO-mediated endothelium-dependent vasomotion), reflecting the functional state of the coronary endothelium, was independent of gender, age, and resting heart conditions. It was modulated by HDL cholesterol levels, even in healthy volunteers, and also related to pharmacologically stimulated vasodilator capacity at the coronary vascular resistance level.


Ring chromosome 14 syndrome presenting with intractable epilepsy: a case report.
Ring chromosome 14 syndrome is a rare genetic disorder. Typically, children with this syndrome have distinct facial features, development delay, microcephaly, seizures, ocular abnormalities, and recurrent respiratory infections. Epilepsy associated with ring chromosome 14 generally shows intractable seizures. We describe a six-month-old girl with ring chromosome 14 syndrome who presented with early-onset and drug-resistant seizures.


Geographic variation in breast cancer mortality for white and black women: 1986-1995.
Breast cancer mortality rates have decreased during the last 20 years in the United States overall. However, declines in breast cancer mortality rates differ among individual states. This analysis ranked states from the highest to the lowest percentage change in mortality between 1986 to 1990 and 1991 to 1995. Data on white and black females were analyzed separately. Among white women, the 10 states showing the greatest percentage change in mortality during those two periods had the greatest baseline mortality in the 1986-to-1990 period. Similarly, the 10 states with the lowest percentage change in mortality had the lowest mortality rate in 1986 to 1990. In contrast, among black women, the top 10 states ranked by percentage change in mortality included either a decline or an increase. The disparities in mortality rates by state likely depend on the stage of disease at diagnoses, socioeconomic status, access to care, and adequacy of medical care.


Dietary vitamin, mineral and herbal supplement use: a cross-sectional survey of before and during pregnancy use in Sydney, Australia.
To describe the use of dietary vitamin, mineral and herbal supplements before and during pregnancy. Pregnant women attending for antenatal care at two tertiary Sydney hospitals between January and March 2014 completed an anonymous survey. Information on general maternal and pregnancy characteristics and the use of dietary and herbal supplements, including type, duration and sources of information, was collected. Frequency and contingency tabulations were performed. A total of 612 women agreed to participate (91% response rate). Of 589 women included in the analysis, mean gestational age at the time of survey was 28.5 weeks (SD 8.3), 55% had no children, and 67% were tertiary-educated. Overall, 62.9% of women reported taking a multivitamin (MV) and/or folic acid (FA) supplement in the 3 months prepregnancy, and 97.5% took a MV and/or FA in the first trimester. At the time of the survey, 93.8% of women were taking at least one supplement (median 2, range 1-13). During pregnancy, 79.1% of women were taking MVs, including 59.2% taking MV only and 19.9% taking MV and FA. The five most common supplements outside of a MV were FA (31%), iron (30%), vitamin D (23%), calcium (13%) and fish oil (12%). Reported herbal supplement rates were low. Folic acid, MVs and other supplements use during and prepregnancy is relatively high, although prepregnancy FA supplementation rates could still be improved. Further research on the actual dosages and dietary intakes consumed is needed to examine whether pregnant women have adequate intake of nutrients, regardless of supplement use.


Ménière's disease.
The authors review some of the contrasts that Ménière's disease presents to the practicing otologist and describe recent findings in electrocochleography (ECochG) and vectornystagmorgraphy that have been of help in establishing the diagnosis in unusual cases. ECochG has also been useful in detecting the presence of the disease in the patient's better ear. The goals of medical and surgical treatment are discussed in relation to these findings.


Future projections of temperature-related excess out-of-hospital cardiac arrest under climate change scenarios in Japan.
Recent studies have reported associations between global climate change and mortality. However, future projections of temperature-related out-of-hospital cardiac arrest (OHCA) have not been thoroughly evaluated. Thus, we aimed to project temperature-related morbidity for OHCA concomitant with climate change. We collected national registry data on all OHCA cases reported in 2005-2015 from all 47 Japanese prefectures. We used a two-stage time series analysis to estimate temperature-OHCA relationships. Time series of current and future daily mean temperature variations were constructed according to four climate change scenarios of representative concentration pathways (RCPs) using five general circulation models. We projected excess morbidity for heat and cold and the net change in 1990-2099 for each climate change scenario using the assumption of no adaptation or population changes. During the study period, 739,717 OHCAs of presumed cardiac origin were reported. Net decreases in temperature-related excess morbidity were observed under higher emission scenarios. The net change in 2090-2099 compared with 2010-2019 was -0.8% (95% empirical confidence interval [eCI]: -1.9, 0.1) for a mild emission scenario (RCP2.6), -2.6% (95% eCI: -4.4, -0.8) for a stabilization scenario (RCP4.5), -3.4% (95% eCI: -5.7, -1.0) for a stabilization scenario (RCP6.0), and - 4.2% (95% eCI: -8.3, -0.1) for an extreme emission scenario (RCP8.5). Our study indicates that Japan is projected to experience a substantial net reduction in OHCAs in higher-emission scenarios. The decrease in risk is limited to a specific morbidity cause, and a broader assessment within climate change scenarios should consider other direct and indirect impacts.


Lithium-induced lung toxicity in rats: the effect of caffeic acid phenethyl ester (CAPE).
We aimed to evaluate the effects of caffeic acid phenethyl ester (CAPE) on lithium (Li)-induced lung toxicity. Twenty-two adult male Wistar albino rats weighing between 280 and 300 g were used. The rats were randomly divided into three groups: control, Li and Li+CAPE groups. Li and CAPE were co-administered intraperitoneally twice daily for 4 weeks. Control rats were given 0.9% NaCl during the same period. All the rats were allowed to feed ad libitum until midnight after they had received the proposed treatment. In the Li group, peribronchial and intraparenchymal lymphocyte and macrophage infiltration were observed. Atypical type II pneumocytes, alveolar destruction and emphysematous changes were also detected. Lymphocyte and macrophage infiltration was significantly decreased in the Li+CAPE group compared with the Li group. Alveolar destruction, emphysematous changes and intraparenchymal mononuclear cell infiltration were also recovered to a level close to the control group. Malondialdehyde (MDA) levels were increased in the Li group compared with the control group. CAPE administration decreased the MDA levels in the Li+CAPE group. CAPE was found to associate with histopathological changes recovery in the lungs and oxidative stress due to Li treatment.


Characteristics of estrogen-2/4-hydroxylase of porcine ovarian follicles: influence of steroidal and non-steroidal agents on the activity of the enzyme in vitro.
The conversion of [3H]estradiol to 2-hydroxyestradiol (2-OH-E2) by homogenates of porcine ovarian follicles was assayed in vitro in the presence and absence of 10 and 100 microM concentrations of the following potential substrates or inhibitors of estrogen-2/4-hydroxylase (E-2/4-H): (1) estrogens; estrone (E1), estriol (E3) and 17 alpha-estradiol (17 alpha-E2), (2) catecholestrogens; 2-hydroxyestradiol (2-OH-E2), 4-hydroxyestradiol (4-OH-E2) and 2-hydroxyestrone (2-OH-E1); (3) 2-methoxyestradiol (2-MeO-E2); (4) halogenated estrogens; 2-bromoestradiol, (2-Bromo-E2) 4-bromoestradiol and 2,4-dibromoestradiol; (5) androgens; testosterone (T), dihydrotestosterone (DHT) and androstenedione; (6) progesterone; (7) epinephrine; (8) inhibitors of steroid aromatase; aminoglutethimide and 4-hydroxyandrostenedione and (9) SKF 525A, an inhibitor of cytochrome P-450. Progesterone and 2-Bromo-E2 were the two most effective inhibitors (2-OH-E2 formation = 4 and 5% of control at 100 microM and 29.6 and 17.4% at 10 microM of progesterone and 2-Bromo-E2, respectively). 2-MeO-E2 at 100 microM was nearly as effective as progesterone in inhibiting E-2/4-H activity but only caused about 50% inhibition at 10 microM. The three catecholestrogens reduced 2-OH-E2 formation to about the same degree (21-23% of control at 100 microM). The 2,4-dibromo-E2 was equipotent with the catecholestrogens while 4-bromo-E2 was about half as effective. The phenolic estrogens, potential substrates for the enzyme, reduced 2-OH-E2 formation to different degrees, with E3 being the most effective. Among the androgens, DHT was almost as effective an inhibitor as the catecholestrogens, T was about half as effective while androstenedione had no effect. Epinephrine and the two inhibitors of aromatase did not inhibit E-2/4-H activity. SKF 525A inhibited E-2/4-H activity but with a potency only about 1/10th that reported for liver.


Balancing psychache and resilience in aging Holocaust survivors.
Psychache can and does co-exist alongside resilience and coping amongst trauma survivors. This has been the center of the a-integrative theory of aging demonstrating an attitude to life based on cognitive and emotional dimensions. Aging of Holocaust survivors (HS) is especially difficult when focus is brought to the issue of integrating their life history. The present study aimed to investigate the interplay between psychache and resilience amongst aging HS. Cross-sectional study of HS and a matched comparison group recruited from the general population was carried out. All underwent a personal interview and endorsed quantifiable psychache and resilience scales. We enrolled 214 elderly participants: 107 HS and 107 comparison participants. Mean age for the participants was 80.7± years; there were 101 women and 113 men in each group. Holocaust survivors did not differ in the level of resilience from comparisons (mean: 5.82 ± 0.68 vs. 5.88 ± 0.55, respectively). Psychache was significantly more intense in the HS group (F(8,205) = 2.21; p < 0.05). The present study demonstrates the complex interplay between psychache and resilience. Aging HS still have to cope with high levels of psychache while realizing a life-long process of development through resilience.


Heightened subjective experience of depression in borderline personality disorder.
Despite the frequent comorbidity of major depression and borderline personality disorder (BPD), limited research has examined what effect this comorbidity has on the severity, course, and presentation of depression. The purpose of this study was to examine whether the severity of major depressive disorder (MDD) in the context of comorbid borderline personality disorder (BPD) differs from MDD when comorbid BPD is not present and to determine whether different measures of depression yield convergent findings. Sixty patients diagnosed with DSM-IV MDD participated in this study. Twenty-nine were diagnosed with DSM-IV BPD, while the remaining 31 had no Axis II diagnosis. Depression was evaluated with both clinician (Hamilton Rating Scale for Depression) and self-report (Beck Depression Inventory) ratings. While the two groups were rated as similarly depressed by clinicians on the overall rating and the factor scores, the MDD/BPD group reported more severe depressive symptoms on the self-report measure. This difference was significant even after controlling for clinician-rated severity. Gender interacted with diagnosis, males in the BPD group showed the largest discrepancies between clinician ratings and self-reports. Posthoc analyses of HDRS factors with the BDI showed that the clinicianrated cognitive disturbance and retardation factors were correlated with self-rated severity overall. Within subgroups, only the retardation factor was correlated with the BDI. Our results suggest that while depressed individuals with and without BPD may be rated as similarly depressed when assessed with objective rating methods, the subjective experience of the depression may be rated as more intense or severe by patients with comorbid BPD. The mechanism underlying this effect remains unknown, and requires further research.


Expression of purinergic receptor channels and their role in calcium signaling and hormone release in pituitary gonadotrophs. Integration of P2 channels in plasma membrane- and endoplasmic reticulum-derived calcium oscillations.
The role of ATP as a positive feedback element in Ca2+ signaling and secretion was examined in female rat pituitary gonadotrophs. ATP and ADP, but not AMP or adenosine, induced a dose- and extracellular Ca2+-dependent rise in [Ca2+]i in identified gonadotrophs in a Mg2+- and suramin-sensitive manner. ATP, adenosine-5'-O-(3-thiotriphosphate), adenosine-5'-O-(1-thiotriphosphate), 2-methylthio-ATP, and 3'-O-(4-benzoyl)benzoyl-ATP were roughly equipotent in rising [Ca2+]i in gonadotrophs, while ADP was effective only at submillimolar concentration range, and none of these compounds permeabilized the cells. On the other hand, alpha,beta-methylene-ATP, beta,gamma-methylene-ATP, and UTP were unable to induce any rise in [Ca2+]i. This pharmacological profile is consistent with expression of P2X2 and/or P2X5 purinergic receptor channels. Patch-clamp experiments showed that ATP induced an inward depolarizing current in gonadotrophs clamped at -90 mV, associated with an increase in [Ca2+]i. The ATP-induced [Ca2+]i response was partially inhibited by nifedipine, a blocker of voltage-sensitive Ca2+ channels (VSCC), but was not affected by tetrodotoxin, a blocker of voltage-sensitive Na+ channels. Thus, the P2-depolarizing current itself drives Ca2+ into the cell, but also activates Ca2+ entry through VSCC. In accord with this, low [ATP] induced plasma membrane-dependent [Ca2+]i oscillations in quiescent cells, and increased the frequency of spiking in spontaneously active cells. ATP-induced Ca2+ influx also affected agonist-induced and InsP3-dependent [Ca2+]i oscillations by increasing the frequency, base line, and duration of Ca2+ spiking. In addition, ATP stimulated gonadotropin secretion and enhanced agonist-induced gonadotropin release. ATP was found to be secreted by pituitary cells during agonist stimulation and was promptly degraded by ectonucleotidase to adenosine. These observations indicate that ATP represents a paracrine/autocrine factor in the regulation of Ca2+ signaling and secretion in gonadotrophs, and that these actions are mediated by P2 receptor channels.


Interferon-tau and pregnancy.
A type I interferon known as IFN-tau is expressed massively by the outer epithelium (trophectoderm) of the preimplantation trophoblast of ruminant ungulate species, such as cattle and sheep, for a few days during early pregnancy. They signal to the mother that she is pregnant and indirectly prevent regression of the corpus luteum so that progesterone production is maintained and normal ovarian cyclicity avoided. Despite their clear roles as reproductive hormones, the IFN-tau have the typical antiviral, antiproliferative, and immunomodulatory activities of other type I IFN. They are most closely related to the 172 amino acid IFN-omega. Unlike other type I IFN, they are not virally inducible and appear to be produced constitutively as the trophectoderm first forms during the development of the blastocyst. The discovery of the IFN-tau illustrates the diverse activities of interferons and their likely involvement in the normal embryonic development of mammals. The diversity of mechanisms different groups of mammals use to prolong the functional life span of the corpus luteum in early pregnancy is probably the consequence of genetic conflict between the genes of the mother and her offspring, which has led to remarkably high rates of change in placental structure and trophoblast signaling mechanisms.


Expression of Toll-like receptor9 in diffuse large B-cell lymphoma: further exploring CpG oligodeoxynucleotide in NFκB pathway.
Human Toll-like receptors (TLRs) that recognize a variety of pathogen-associated molecular patterns are associated with activation and immunogenic response in lymphoid neoplasms, but rarely explored in diffuse large B-cell lymphoma (DLBCL). We conducted this study to evaluate the expression of TLR9 in and potential treatment of DLBCL with TLR9 agonist - CpG oligodeoxynucleotide (ODN). The real-time quantitative reverse transcription-polymerase chain reaction was carried out to detect TLR9 expression in 41 formalin-fixed paraffin-embedded samples. The transformation of immunophenotype and NFκB pathway of DLBCL upon CpG ODN stimulation were investigated by a DLBCL cell line. TLR9 was commonly detected in DLBCL with relative mRNA levels above 1.0 × 10(-2) in 35 of 41 cases (85.36%). It was suspected that a high proportion of DLBCL to be activated by CpG stimulation. In vitro study with a DLBCL cell line revealed an increased CD20, but decreased BCL-6 and MUM1/IRF4 expression after treatment with CpG ODN. The NFκB pathway was initially activated, but finally suppressed upon CpG ODN stimulation. The proliferation of tumor cells was also inhibited by long time incubation. These findings provide new insights into the role of TLR9 in DLBCL and potential implication of TLR9 agonist in the treatment of DLBCL.


Fecal estradiol-17β and testosterone in prepubertal domestic cats.
The aim of this article was to describe the time course of prepubertal sexual steroids in domestic cats. Fourteen newborn kittens were followed up until puberty (physical, behavioral, and hormonal changes). Fecal testosterone [T; males] and E estradiol 17-β [E2; females] concentrations were analyzed by repeated measures ANOVA and two consecutive time windows (TWs) were used to compare changes in both male (postnatal weeks 1-4 vs. 5-14) and females (postnatal weeks 1-5 vs. 6-13). Puberty was achieved 14.3 ± 0.3 and 13.3 ± 0.4 weeks after birth in male and female cats, respectively. In both genders, during TW-1 fecal steroids concentrations were similar (males) or even higher (females) to that previously described for mature cats. Fecal T (P < 0.01) and E2 (P < 0.01) varied throughout the weeks. Differences were found when hormonal concentrations of TW-1 were compared with those of TW-2 both for male (61.4 ± 7.9 vs. 16.9 ± 2.2 ng/g; P < 0.01) and female (78.2 ± 12.5 vs. 11.2 ± 4.0 ng/g; P < 0.01) cats. It is concluded that in domestic cats there is a sexual steroid surge during the first 4 and 5 postnatal weeks in male and female animals, respectively.


A nonlinear least squares program based on differential equations, MULTI (RUNGE), for microcomputers.
A nonlinear least squares program based on first-order simultaneous differential equations, MULTI (RUNGE), for personal computers was developed. Four algorithms, i.e. the classical Gauss-Newton method, the damping Gauss-Newton method, the modified Marquardt method and the simplex method can be used for the nonlinear curve fitting in MULTI (RUNGE). The differential equations and the initial conditions which are voluntarily defined by the user are numerically solved by the Runge-Kutta-Gill method and the numerically integrated solutions are fitted to the observed data points by the iterative least squares algorithms. MULTI (RUNGE) can be executed on many personal computers without any modification, because this program is written in the Microsoft minimum BASIC commands alone. The dimensions of differential equations, the number of parameters to evaluate and the number of experimental data points are restricted only by the available memory in computers and by the computing time.


Assessment the performance of classification methods in water quality studies, A case study in Karaj River.
To show the performance of classification methods in water quality studies, linear discriminant, and Naïve Bayesian classification methods were applied at nine sampling stations with respect to four parameters including COD, nitrite, nitrate, and total coliforms (selected from ten water quality variables) in Karaj River, Iran. To fulfill the goals of this study, the sampling stations were first separated into two groups using cluster analysis. Rural wastewater was the main source of pollution in the first group, whereas the quality of water in the second group has been degraded mainly by organic and agricultural pollution. In order to have an independent group against which the performance of other classification methods is considered, three cross-validation methods including twofold, leave-one-out, and holdout methods were utilized to retain an independent test set. The results of cross-validation for the linear discriminant analysis show that, except for the leave-one-out method with 11.1 % misclassification error, the overall performance has been the same as that of the training data set. Therefore, it has outperformed compared with that of Naïve Bayesian classification method. However, even though in situations where the correlation coefficient among the parameters is low, the latest method can offer the same performance as that of linear discriminant analysis as well. A sensitivity analysis was implemented using ten water quality variables (pH, COD, EC, TDA, turbidity, nitrate, nitrite, sulfate, TC, and FC) to find the most important variables in the classification of Karaj River showing that turbidity, next to COD, pH, nitrate, and sulfate, have had the most contribution in this field.


Free thyroxin measured in dried blood spots from normal, low-birth-weight, and hypothyroid neonates.
We have adapted a new radioimmunoassay for free thyroxin (FT4) measurement in dried blood spots for use in neonatal screening for hypothyroidism. The method is easy, fast, and cheap. Within-assay and between-assay CVs are respectively 9.6% and 13.2%. In 997 neonates three days postpartum with normal thyrotropin concentrations, the mean FT4 concentration was 27.2 pmol/L (SD 7.3 pmol/L). There was no significant difference in mean FT4 concentration between boys and girls. FT4 concentrations increased linearly with birth weight or with gestational age, as expressed by multiple linear regression: FT4 (pmol/L) = 0.0016 birth weight (g) + 0.6931 gestational age (weeks) - 4.8772. Only gestational age significantly affected the FT4 value. For five hypothyroid infants tested on day three postpartum, FT4 values were all below the 1st percentile of values from healthy neonates. Thus, when the neonatal concentration of thyrotropin is above normal, FT4 measured in the same sample can provide a reliable earlier diagnosis of hypothyroidism.


The use of an objective structured clinical examination with postgraduate residents in pediatrics.
To evaluate the usefulness of an objective structured clinical examination (OSCE) for assessing and providing feedback to postgraduate residents in pediatrics. A 5-station OSCE given in 1996, based on the educational objectives of a general pediatric training program. Each station assessed the residents' interviewing and history-taking skills with a standardized patient. The results were correlated with those of the in-training evaluation reports. The Department of Paediatrics, University of Toronto Faculty of Medicine, Toronto, Ontario. Forty-three of 61 pediatric residents: 14 first-year, 12 second-year, 8 third-year, and 9 fourth-year residents. Scores for each of the 5 stations were broken down into 15 points for the check-list, 5 for the global assessment, and 10 for the written postencounter question, for a total score of 150. The in-training evaluation report ratings were converted to a 5-point numerical scale, ranging from 1 (unsatisfactory) to 5 (outstanding). The mean OSCE score for the 43 pediatric residents was 104.9. Although the residents in their senior year scored higher, there was no statistically significant difference among the 4 years for the total OSCE score or for any of the 5 stations. The fourth-year residents' scores on the postencounter questions were significantly (P < .05) higher than the first-year residents' scores. Two residents scored less than 60%. The internal consistency of the 5-station OSCE was limited (r = 0.69). Residents received verbal feedback at the conclusion of the OSCE, and they received their scores when they were calculated. The mean overall in-training evaluation report score for all 61 pediatric residents was 3.9. There was a moderate, but statistically significant, correlation between the overall mean OSCE results and the overall mean in-training evaluation report scores (r = 0.45). The OSCE can provide a useful formative evaluation of postgraduate residents, but the usefulness of the evaluation data and the feedback must be balanced with the logistic difficulties and expense.


Effects of blood pressure and sex on heart-vessel coupling in essential hypertension.
This study aimed to investigate the impact of blood pressure and sex on heart-vessel coupling in patients with essential hypertension via ultrasound. We studied 76 patients with essential hypertension (48 males and 28 females) and 65 healthy controls (33 males and 32 females). Coupling parameters were obtained using ultrasound technology combined with brachial artery blood pressure measurement. The Ea and Ees were higher in the hypertension group than in the control group (P < 0.01), with no statistically significant difference in Ea/Ees between the two groups (P >0.05). After subjects were classified by sex, the Ea and Ees of males and females in the hypertension group were higher than those in the control group (P < 0.05 or P < 0.01), while the Ea/Ees was lower in hypertensive females than in control females (P < 0.05). In female patients with essential hypertension, heart-vessel coupling was easily damaged, and systolic blood pressure was associated with heart-vessel coupling damage to some extent.


[Osteochondroma as an unusual cause of metatarsus primus varus].
A solitary osteochondroma of the metatarsale II of an adolescent is presented which led to a painful Metatarsus primus varus. After resection of the tumor the patient was free of symptoms, the postoperative resulting form of the foot was normal. One should be aware of a tumor as a possible cause of foot deformities.


High-resolution ultrasound in assessment of the gastrointestinal tract.
Ultrasound (US) is frequently the first investigation performed in patients presenting with a variety of abdominal symptoms, and there is a growing appreciation of its value in a wide range of gastrointestinal (GI) disorders. The advantages of US are that it is quick, safe, readily available, noninvasive, and avoids ionizing radiation. It is now the primary imaging investigation when conditions such as appendicitis and hypertrophic pyloric stenosis (HPS) are suspected. For the diligent examiner careful assessment of the bowel can be rewarding either by diagnosing bowel pathology or identifying possible pathology and determining the most appropriate sequence of diagnostic investigations. Its real time capabilities are of particular usefulness in abdominal conditions; clinical correlation is instant and features such as peristalsis and bowel compressibility can be readily assessed. This review describes and illustrates the current role of high-resolution transabdominal US in the detection of GI pathology with discussion on some of the applications of endoscopic ultrasound (EUS) as they relate to this topic.


The Cayapa Indians of Ecuador: a genetically isolated group with unexpected complement C7 M/N allele frequencies.
The Cayapa Indians live in north-western Ecuador in close proximity to a Black population of African ancestry. C7 M/N allotyping has proved to be a good technique for plasma genetic analysis in several populations. Investigation of 124 Cayapa plasma samples revealed the highest allele frequency of C7*N observed in any population examined so far (0.36 versus 0.225 or lower). The marked difference in frequency compared with several Oriental populations, which are believed to have been derived from the same Asian population as native Amerindians, may reflect the effect of a small founder population followed by a high degree of genetic isolation. The allele frequency of 0.12 for C7*N determined for the neighbouring Black population supports the conclusion that there has been a lack of genetic admixture of Cayapas with other populations, confirming the results of ethnohistorical investigations and other protein polymorphism studies.


[Kinetics of electron transfer in macromolecules].
With the help of retarded double-time Green function technique a method of estimation of electron transfer rate in protein macromolecules has been developed. Possible experimental test is suggested.


Symmetry in locomotor central pattern generators and animal gaits.
Animal locomotion is controlled, in part, by a central pattern generator (CPG), which is an intraspinal network of neurons capable of generating a rhythmic output. The spatio-temporal symmetries of the quadrupedal gaits walk, trot and pace lead to plausible assumptions about the symmetries of locomotor CPGs. These assumptions imply that the CPG of a quadruped should consist of eight nominally identical subcircuits, arranged in an essentially unique matter. Here we apply analogous arguments to myriapod CPGs. Analyses based on symmetry applied to these networks lead to testable predictions, including a distinction between primary and secondary gaits, the existence of a new primary gait called 'jump', and the occurrence of half-integer wave numbers in myriapod gaits. For bipeds, our analysis also predicts two gaits with the out-of-phase symmetry of the walk and two gaits with the in-phase symmetry of the hop. We present data that support each of these predictions. This work suggests that symmetry can be used to infer a plausible class of CPG network architectures from observed patterns of animal gaits.


Depressed myocardial contractile reserve in patients with obstructive sleep apnea assessed by tissue Doppler imaging with dobutamine stress echocardiography.
Hypoxia has been suggested to affect myocardial contractile function in patients with obstructive sleep apnea (OSA). We sought to determine whether myocardial contractile reserve (MCR), as evaluated by echocardiographic tissue Doppler imaging with dobutamine stress (TDDS), might be depressed in OSA patients. Thirty patients with suspected OSA (25 men and 5 women; mean age, 51 +/- 11 years [+/- SD]) underwent overnight polysomnography and TDDS. Peak myocardial systolic velocity (Sm) and peak myocardial early diastolic velocity (Em) in the 12 myocardial segments of the left ventricular (LV) walls were averaged, and the mean Sm and Em during TDDS were compared between patients with apnea-hypopnea index (AHI) <15/h (group 1, n = 13) and those with AHI >/= 15/h (group 2, n = 17). MCR was calculated as the difference between the resting and peak Sm during TDDS. In both groups, Sm increased dose dependently during TDDS. However, the relative increase in Sm was significantly lower in group 2, resulting in a lower value of MCR (5.5 +/- 1.2 cm/s vs 7.4 +/- 1.3 cm/s, p < 0.001). The Em was lower in group 2 compared with group 1 throughout TDDS. MCR was correlated significantly with AHI (r = - 0.67, p < 0.0001), resting Em (r = 0.53, p < 0.005), and body mass index (r = - 0.46, p < 0.05) independent of the LV mass index. OSA can affect MCR, implying an etiologic contribution from repetitive hypoxic events. TDDS could identify subtle abnormalities of OSA-related cardiac involvement.


Microstructural analysis of severe bone lesions in seven thalassemic patients treated with deferoxamine.
Osteochondrodystrophic lesions, mainly affecting long bone metaphyses, can be radiologically evident in homozygotic thalassemic patients treated with deferoxamine, and their incidence rate varies among authors. The clinical and radiological appearance of these lesions is described in the literature, but microstructural data are still lacking. The aim of our research was to evaluate the microstructure of five tibial biopsy specimens from thalassemic patients with bone lesions (5 cases out of 180 patients followed for the last 10 years, i.e., 2.8%) and two bone biopsy specimens from thalassemic patients with no radiological alteration of the long bones. As control, bone tissue taken from autoptic tibiae of two subjects with no skeletal pathology was used. Using microradiography and X-ray diffraction (XRD), we found a reduced and irregular mineralization of the bone (compared with controls) in thalassemic subjects. Bone tissue microhardness was also significantly reduced. Nevertheless, bone apatite lattice was unaltered and no 'foreign' crystallographic phase was recorded by XRD. In conclusion, all the patients shared a similar picture of abnormal bone, even with no radiological evidence of lesion.


Nodular mucinosis of the breast: a case report with pathologic, ultrasonographic, and clinical findings and review of the literature.
Nodular mucinosis is an extremely rare breast lesion. This benign mass usually presents clinically as a poorly circumscribed, subareolar, myxoid mass in young female patients. We report a case of this rare breast lesion and discuss its clinical, radiologic, and histopathologic features. A 21-year-old white woman presented with a mass in the left breast of 6 months' duration. She had never been pregnant or had any history of breast feeding, surgery, trauma, or use of exogenous hormones or a family history of breast cancer. Clinical breast examination demonstrated a 1 cm "rubbery" mass directly under and continuous with the left nipple. The skin that covered the mass had an edematous and irregular appearance without erythema or drainage from the nipple. Ultrasonography demonstrated a 1-cm, nonintraductal, circumscribed, homogeneous, isoechoic mass that was continuous or part of the base of the left nipple. The mass was smooth, with a thin echogenic rim. Doppler flow showed some vascularity. These findings suggested a benign breast lesion, including a fibroadenoma or nipple adenoma. Despite reassurance, the patient desired excision of the lesion. Gross examination revealed a nodular, rubbery-firm, ovoid, pink, polypoid mass that measured 1.5 x 0.9 x 0.8 cm. Microscopic examination showed a well-circumscribed tumor with a nodular appearance, which consisted of an accumulation of pink myxoid tissue and contained spindle cells with bland-appearing nuclei, no mitosis, and mild cellularity. The pink myxoid tissue was stained with Hale colloidal iron and Alcian blue. The Alcian blue stain was removed by pretreatment with hyaluronidase. The spindle cells stained with vimentin and smooth muscle actin; however, they did not express smooth muscle myosin or cytokeratin. This report presents and discusses the pathologic, ultrasonographic, and clinical findings of this rare entity.


The impact of aging on sexual function in women and their partners.
Aging has a powerful impact on the quality of relationship and sexual functioning. The psychological impact of aging after midlife is a particularly timely topic, given improved medical and psychological understanding of sexuality in both women and men as well as significant improvement in the conceptualization of female sexuality and evolving treatment advances for female sexual dysfunctions. It is time to dispel the stereotype of the midlife woman in order to more effectively address emotional and sexual issues arising in her relationships. Regardless of the length or nature of the relationship, its quality is enhanced by emotional intimacy, autonomy without too much distance, an ability to manage stress, and to maintain a positive perception of self and the relationship. To understand and treat effects of aging on sexuality, it is important to address the three components of sexual desire: drive, beliefs/values, and motivation, as well as the social context of a woman's life. It is also essential to understand how the physiological changes in female as well as male sexual functioning impact desire. Further, other health-related changes that occur with aging must be recognized and addressed.


Overexpression of Psoriasin (S100A7) Contributes to Dysregulated Differentiation in Psoriasis.
Psoriasin, which is highly expressed in psoriasis, is encoded by a gene located within the epidermal differentiation complex. The aim of this study was to investigate the effect of endogenous psoriasin on disturbed keratinocyte differentiation in psoriasis. Immunohistochemical staining revealed a gradient of psoriasin expression in the psoriatic epidermis with highest expression in the suprabasal, differentiated layers. Induction of keratinocyte differentiation caused concurrent expression of psoriasin and the differentiation marker involucrin. The differentiation-induced psoriasin expression was found to be mediated by the protein kinase C pathway. The downregulation of psoriasin expression by small interfering RNA revealed that psoriasin mediates the expression of involucrin, desmoglein 1, transglutaminase 1 and CD24 in normal differentiation. The lentivirus-mediated overexpression of psoriasin, mimicking the psoriatic milieu, gave rise to an altered regulation of differentiation genes and an expression pattern reminiscent of that in psoriatic epidermis. These findings suggest that psoriasin contributes to the dysregulated differentiation process in the psoriasis epidermis.


Human immunodeficiency virus isolates from asymptomatic homosexual men and from AIDS patients have distinct biologic and genetic properties.
Human immunodeficiency virus type 1 (HIV-1) isolates from asymptomatic homosexual men and AIDS patients were compared for their in vitro biologic and genetic properties. Most of the HIV-1 isolates from asymptomatic men, but not from AIDS patients, failed to infect CD4+ H9 cells and phytohemagglutinin-stimulated peripheral blood lymphocytes. In a longitudinal study, serial HIV-1 isolates obtained from men who seroconverted to HIV-1 and later developed AIDS were able to infect H9 cells. In contrast, longitudinal isolates from men who remained asymptomatic did not infect H9 cells. HIV-1 isolates from AIDS patients in general exhibited increased production of intracellular viral DNA, RNA, and protein as compared to isolates from asymptomatic men. Cells infected with HIV-1 isolates from asymptomatic men produced very little gp120, p24, and p55 proteins as compared to those from AIDS patients. The overall restriction patterns of HindIII, Sac-1, Pst-1, EcoR1, and BamH1 were very similar between HIV-1 isolates from asymptomatic men and those from AIDS patients. However, the restriction endonuclease pattern of BglII was quite distinct for isolates from asymptomatic men as compared to AIDS patients. Preliminary studies mapped a unique BglII site in the gag region of most of the isolates from asymptomatic men, approximately 2.0 kb from the 5' end. Thus, HIV-1 isolates from asymptomatic subjects and from AIDS patients have distinct biologic and genetic properties which may be related to the various clinical outcomes of HIV-1 infection.


Inclusion body myositis: a degenerative muscle disease associated with intra-muscle fiber multi-protein aggregates, proteasome inhibition, endoplasmic reticulum stress and decreased lysosomal degradation.
Sporadic inclusion body myositis (s-IBM), the most common muscle disease of older persons, is of unknown cause, and there is no enduring treatment. Abnormal accumulation of intracellular multi-protein inclusions is a characteristic feature of the s-IBM phenotype, and as such s-IBM can be considered a "conformational disorder," caused by protein unfolding/misfolding combined with the formation of inclusion bodies. Abnormal intracellular accumulation of unfolded proteins may lead to their aggregation and inclusion body formation. The present article is focusing on the multiple proteins that are accumulated in the form of aggregates within s-IBM muscle fibers, and it explores the most recent research advances directed toward a better understanding of mechanisms causing their impaired degradation and abnormal aggregation. We illustrate that, among other factors, abnormal misfolding, accumulation and aggregation of proteins are associated with their inadequate disposal-and these factors are combined with, and perhaps provoked by, an aging intracellular milieu. Other concurrent and possibly provocative phenomena known within s-IBM muscle fibers are: endoplasmic reticulum stress and unfolded protein response, mitochondrial abnormalities, proteasome inhibition, lysosome abnormality and endodissolution. Together, these appear to lead to the s-IBM-specific vacuolar degeneration, and muscle fiber atrophy, concluding with muscle fiber death.


Rapid kinetics of alpha 2-adrenergic inhibition of adenylate cyclase. Evidence for a distal rate-limiting step.
Activation and inhibition of adenylate cyclase in the presence of GTP, the natural guanine nucleotide regulator, are too fast to study by standard biochemical methods. In order to identify the rate-limiting steps in adenylate cyclase regulation, we measured the kinetics of stimulation and inhibition of the enzyme on a subsecond to second time scale using a novel rapid-mix quench technique. Even using our rapid-mix quench method, activation by PGE1 and forskolin was instantaneous (cAMP accumulation was linear between 0.5 and 30 s). In contrast, we found a lag period of 1.2-10 s for epinephrine-mediated inhibition. The length of the lag depended on the concentration of GTP and monovalent cations present. In the absence of NaCl, the rate constant for the onset of inhibition (kinh) increased only slightly with GTP concentration saturating at a value of 0.16 s-1 (t1/2 4.3 s) at 1 microM GTP. In the presence of 100 mM NaCl, kinh was strongly dependent on GTP concentration, reaching a maximum value of 0.57 s-1 (t1/2 1.2 s) at 100 microM GTP. Thus, activation of both Gi and Gs in intact platelet membranes is much faster (t1/2 less than 5 s) than previously reported for reconstituted systems. Also, the strong dependence of the rate of adenylate cyclase inhibition on GTP concentration implies that the rate-limiting step in inhibition is distal to GTP binding. The effect of NaCl to increase the maximal rate of inhibition is specific for sodium since KCl has no effect on kinh.(ABSTRACT TRUNCATED AT 250 WORDS)


Bexarotene: a clinical review.
Bexarotene (Targretin, Ligand Pharmaceuticals Inc.) is a synthetic retinoid analog with specific affinity for the retinoid X receptor and belongs to a group of compounds called rexinoids. Early clinical trials of this drug demonstrated activity in cutaneous T-cell lymphoma. Subsequent Phase II/III trials have demonstrated a greater than 50% response rate in patients with all stages of cutaneous T-cell lymphoma who were refractory or intolerant to the previous therapy. The principal toxicities of bexarotene include central hypothyroidism, xeroderma and elevation of cholesterol and triglycerides. These toxicities can be managed with dose attenuation or addition of atorvastatin (Lipitor, Pfizer) or fenofibrate (TriCor, Abbott Laboratories). Since bexarotene has little bone marrow toxicity, it is an excellent candidate for combination therapy with other modalities useful in the treatment of cutaneous T-cell lymphoma. These include ultraviolet B irradiation, psoralen and ultraviolet A photochemotherapy, interferons, denileukin diftitox (Ontak, Ligand Pharmaceuticals Inc.) and cytotoxic chemotherapy. Bexarotene has also been investigated in the treatment of breast cancer and non-small cell carcinoma of the lung with promising early results.


Biodegradation and chiral stability of fipronil in aerobic and flooded paddy soils.
Microbiological degradation of the racemic mixture, the enantiopure R- and S-fipronil was examined under both aerobic and flooded conditions in three Chinese paddy soils. The degradation kinectics and enantiomer fraction (EF) were determined by means of high-performance liquid chromatography (HPLC) with chiral Chiralcel OD-H column, while desulfinyl, sulfone and sulfide derivatives were monitored by reversed phase HPLC with diode array detection (DAD). The degradation/transformation of enantiomers of fipronil in the three live soils under aerobic and flooded conditions generally complied with the first-order kinetics (R2 > or = 0.94). The calculated t1/2 values of the enantiomers of fipronil ranged between 21 and 34 days for aerobic incubation experiments and between 8 and 19 days under flooded conditions incubation, respectively. The calculated EF values of fipronil during the incubation time were all close to 0.5, indicating that the degradation/transformation of fipronil was almost nonenantioselective. The main metabolites of fipronil formed in the incubation experiments were sulfone and sulfide derivatives by oxidative and reductive processes, respectively. The oxidative pathway seemed more active. Under flooded conditions, S-fipronil was preferentially degraded in the three soil samples used. The main metabolite was determined as fipronil sulfide. In control experiments, almost no removal of enantiomers of fipronil was observed indicating that the degradation of fipronil in the paddy soil used was attributed to microbial mediated processes under both aerobic and flooded conditions. In addition, no enantiomerization of fipronil was observed in the soil samples examined under both aerobic and flooded conditions. These results for major differences in the degradation of the enantiomers as well as the formation of toxic metabolites may have some implications for better environmental and ecological risks assessment for chiral pesticides.


Link between glycation and lipoxidation in red blood cells in diabetes.
Oxidative stress is postulated to be increased in patients with diabetes mellitus. Glycation enhanced by elevated glucose concentrations may induce the formation of oxygen-derived free radicals (OFRs). OFRs would cause oxidative damage to endogenous molecules, including cholesterol. Accumulating evidence suggests that oxidative cell injury caused by OFRs contributes to the development of both macroangiopathy and microangiopathy in diabetes. Our previous studies have shown that 7-keto cholestadien is one of the major products of cholesterol peroxidation in diabetic erythrocyte membrane and its levels correlate with hemoglobin Alc (HbAlc) values. We have newly identified 3-cholesten-6-one, one of the minor products of cholesterol peroxidation, in it. The aim of our study is to investigate whether 3-cholesten-6-one levels also correlate with HbAlc values. Levels of 3-cholesten-6-one were assessed in erythrocyte membrane lipid by monitoring peak areas of 3-cholesten-6-one to cholesterol with gas chromatography-mass spectrometry. The peak area ratio of 3-cholesten-6-one to cholesterol was used as a marker of cholesterol peroxidation. The HbAlc value, an index of both glycemic stress and glycation, was measured by high-performance liquid chromatography. In this study, we evaluated 33 diabetic and 29 healthy subjects, matched for age (59.3+/-14.5 vs. 57.3+/-13.7 years, mean+/-S.D.) and sex (15 males and 14 females vs. 16 males and 17 females). There were both significantly raised HbAlc levels (4.6+/-0.8 vs. 8.3+/-2.4%, P<0.001) and significantly increased ratios of 3-cholesten-6-one to cholesterol (0.2+/-0.4 vs. 21+/-1.8, P<0.001) in diabetic patients compared to control subjects. A good correlation between HbAlc levels and ratios of 3-cholesten-6-one to cholesterol was found in participants (r = 0.75, P<0.001, y = 0.46x-1.8). This suggests that an oxidative stress exists in diabetes and the link between glycation and lipoxidation is found in diabetic red blood cell.


Optical electric-field sensor based on angular optical bias using single β-BaB2O4 crystal.
A novel optical electric-field sensor is proposed and demonstrated in experiment by use of a single beta barium borate (β-BaB2O4, BBO) crystal. The optical sensing unit is only composed of one BBO crystal and two polarizers. An optical phase bias of 0.5π is provided by using natural birefringence in the BBO crystal itself. A small angle (e.g., 0.6°) between the sensing light beam and principal axis of the crystal is required in order to produce the above optical bias. Thus the BBO crystal is used as the electric-field-sensing element and quarter waveplate. The ac electric field in the range of (1.4-703.2) kV/m has been measured with measurement sensitivity of 1.39 mV/(kV/m) and nonlinear error of 0.6%. Compared with lithium niobate crystal used as an electric-field sensor, main advantages of the BBO crystal include higher measurement sensitivity, compact configuration, and no ferroelectric ringing effect.


Functional dissection of 5' and 3' extragenic control regions of human tRNA(Val) genes reveals two different regulatory effects.
Two natural human tRNA(Val) genes, pHtV1 and pHtV3, differ in their transcription efficiency by an order of magnitude. The extragenic control regions (ECRs) responsible for this effect were compared with respect to the kinetics and thermodynamics of transcription complex formation. The 5' ECR of pHtV1 acts by increasing both the rate of stable complex formation and the equilibrium constant of association between tDNA and at least one transcription factor present in the stable complex. The stability of the preinitiation complexes is not affected by ECRs. For the formation of a stable preinitiation complex, we suggest a two-step mechanism, comprising (i) the ECR-controlled association of at least one transcription factor (TFIIIC) with the tDNA, and (ii) an ECR-independent conformational change of this tDNA-protein complex. The function of 3' ECRs could be discriminated from the 5' ECR-mediated effects by transcriptional analysis of two chimeric constructs derived from pHtV1 and pHtV3. Surprisingly, the pHtV1 3' ECR causes an eight-fold increase of transcription efficiency, although it has only minor influence on stable preinitiation complex formation. Instead, this ECR stimulates transcription by promoting the transition of the preinitiation complex into an activity synthesizing transcription complex. This novel function of a 3' ECR contributes an additional regulatory level for tRNA gene expression.


[General anesthesia and bronchoscopy].
High frequency, positive pressure ventilation during anesthesia for bronchoscopy, uses the intermittent delivery of oxygen and an anesthetic gas mixture thus avoiding the risks of hypoxia, retention of carbon dioxide and concomitant acidosis. This technique may be used with low pressures in the airways (8 to 10 cm of water during insufflation).


Flow dynamic effect of the anastomotic angle: a numerical study of pulsatile flow in vascular graft anastomoses models.
Pulsatile non-Newtonian blood flow in three distal end-to-side anastomoses models of prosthetic grafts has been analysed applying computer simulation. The anastomotic angles of the three-dimensional geometric models vary over 30°, 45° and 60°. The pulsatile inflow conditions in the graft remain unchanged. Numerical results are presented for the axial and the secondary flow velocity and the wall shear stress distribution. Further, the paths of fluid particles and the particle residence times are demonstrated by means of numerical flow visualization. The quantitative study shows complex flow and wall shear stress patterns with flow separation and strong secondary motion in the host vessel and a weakly migrating flow stagnation point on the arterial floor during the entire pulse cycle in the models under consideration. The flow dynamic effects, which seem to be important in the development of intimal hyperplasia, are dependent on the anastomotic angle and increase with increasing angle.


Comparison of Patterns of Physical Activity and Sedentary Behavior Between Children With Cerebral Palsy and Children With Typical Development.
Reduced participation in physical activity and increased time spent in sedentary behavior are associated with overweight, chronic disease, and disability. In order to optimize recommendations and interventions to increase physical activity and reduce sedentary behavior in children with cerebral palsy (CP), knowledge of their physical activity and sedentary behavior is needed. The aim of this study was to describe light, moderate, and vigorous physical activity and sedentary behavior in preadolescent children with and without CP and compare physical activity and sedentary behavior between the 2 groups. This was a cross-sectional study of 33 children, aged 6 to 10 years, with CP (Gross Motor Function Classification System [GMFCS] levels I-III) and 33 age- and sex-matched children with typical development. Physical activity was measured using the RT3 accelerometer over 7 days. Children with CP spent more time in sedentary behavior and accumulated less total activity, moderate activity, vigorous activity, and sustained bouts of moderate-to-vigorous activity (MVPA). They also accumulated a fewer number of bouts of MVPA and vigorous activity, despite spending a similar amount of time in each bout. The small number of children in GMFCS levels II and III did not allow for adjustment for GMFCS level when comparing physical activity between children with and without CP. Preadolescent children with CP spent less time in moderate and vigorous activity and more time in sedentary behavior than children with typical development. Children with CP also accumulated less continuous MVPA and vigorous activity as a result of achieving fewer sustained bouts of MVPA and vigorous activity throughout the day.


Association of complement factor H Y402H gene polymorphism with Alzheimer's disease.
Alzheimer's disease (AD) and age-related macular degeneration (AMD) share several epidemiological and biochemical features. The present study aimed to assess the possible influence of the AMD-associated complement factor H (CFH) Y402H (1277T > C) polymorphism on the risk of AD. Caucasian subjects (n = 800) meeting the criteria for probable (n = 717) or definite (n = 83) AD and Caucasian non-demented controls (n = 1265) were included in this multi-center case-control study, in which genotype and allele frequencies of the CFH 1277T > C polymorphism were determined and related to diagnosis, APOE genotype, Mini-Mental State Examination score (MMSE) and the cerebrospinal fluid (CSF) biomarkers total-tau (T-tau), phospho-tau(181) (P-tau(181)), and beta-amyloid(1-42) (Abeta(1-42)). The AMD-associated CFH genotypes (1277CC and 1277TC) were overrepresented in subjects with AD as compared to control individuals (P = 0.029). Positive C carrier status was associated with an odds ratio (OR) for AD of 1.24 (95% confidence interval [CI] 1.02-1.50). When APOE epsilon4 carrier status was included in the regression model, this association was even stronger (OR 1.34, 95% CI: 1.08-1.65, P = 0.007). Subgroup analysis showed that the association between CFH C allele positivity and AD was only evident for individuals carrying the APOE epsilon4 allele. Positive C carrier status was also associated with lower levels of CSF Abeta(1-42) selectively in the control group in an APOE epsilon4-independent manner (P = 0.003). In conclusion, the CFH 1277T > C polymorphism seems to influence the risk of AD and there appears to be an interaction between CFH 1277C and APOE epsilon4 alleles. The CFH 1277C allele may predispose patients for co-morbidity in AD and AMD.


Linking women-led community kitchens to school food programmes: lessons learned from the Healthy Kitchens, Healthy Children intervention in Palestinian refugees in Lebanon.
Decades of marginalization have led Palestinian refugees living in Lebanon to experience multigenerational poverty and food insecurity. The Healthy Kitchens, Healthy Children programme implemented and examined the impact of a two-pronged intervention that employed women through community kitchens to deliver a subsidized healthy daily school snack to elementary-school children in Palestinian refugee camps in Lebanon. We describe the rationale, study design, theorized impact pathways, and discuss lessons learned. The programme was quasi-experimental. We conducted formative and process evaluation of both components of the intervention to elucidate the pathways to programme impact. Palestinian refugee camps in Lebanon. Thirty-three women participated in the kitchens and provided subsidized snacks to 714 children. Snacks were healthy, traditional Palestinian recipes designed by women and a nutritionist. Participation fluctuated but eventually increased after modifying the meals to ensure acceptability by children. The main challenges to sustainability related to the need for subsidization of the meals and the lack of school policies around the regulation of sales of school food, which together led to fluctuations in programme participation. The study provides lessons learned on the potential of this model to improve the human capital of two generations of protracted refugees. The availability of schools as a constant market for these social enterprises offers an opportunity for sustainable livelihood generation and food security gains. Challenges to sustainability remain and could be addressed through social (subsidies to support the programme) and structural (policies to restrict unhealthy food sales) measures.


Identification of disease-associated DNA methylation in B cells from Crohn's disease and ulcerative colitis patients.
Changes in the methylation status of inflammatory bowel disease (IBD)-associated genes could significantly alter levels of gene expression, thereby contributing to disease onset and progression. We previously identified seven disease-associated DNA methylation loci from intestinal tissues of IBD patients using the Illumina GoldenGate BeadArray assay. In this study, we extended this approach to identify IBD-associated changes in DNA methylation in B cells from 18 IBD patients [9 Crohn's disease (CD) and 9 ulcerative colitis (UC)]. B cell DNA methylation markers are particularly favorable for diagnosis due to the convenient access to peripheral blood. We examined DNA methylation profiles of B cell lines using the Illumina GoldenGate BeadArray assay. Disease-associated CpGs/genes with changes in DNA methylation were identified by comparison of methylation profiles between B cell lines from IBD patients and their siblings without IBD. BeadArray data were validated using a bisulfite polymerase chain reaction (PCR)-based restriction fragment length polymorphism (RFLP) method. To verify that observed changes in DNA methylation were not due to virus transformation, we compared specific CpG DNA methylation levels of GADD45A and POMC between B cell lines and matching peripheral blood B lymphocytes from five individuals. Using this approach with strict statistical analysis, we identified 11 IBD-associated CpG sites, 14 CD-specific CpG sites, and 24 UC-specific CpG sites with methylation changes in B cells. IBD- and subtype-specific changes in DNA methylation were identified in B cells from IBD patients. Many of these genes have important immune and inflammatory response functions including several loci within the interleukin (IL)-12/IL-23 pathway.


Polymyositis in an immunodeficiency disease in monkeys induced by a type D retrovirus.
Fifty percent of primates with acquired immunodeficiency caused by a well-characterized type D retrovirus (SAIDS D) developed clinical, laboratory, and histologic features of polymyositis. By use of specific antisera and immunochemical techniques, we found the virus in the lymphoid cells surrounding muscle fibers and invading the endomysia septa. SAIDS D virus was isolated from the involved muscles and infected myotubes of normal muscle in tissue culture. These results suggest that retroviruses, a group of viruses increasingly associated with human diseases, can cause polymyositis with immunodeficiency in nonhuman primates and could play a role in human polymyositis.


From gallstones to genes: two hundred years of sterol research. A tribute to George J. Schroepfer Jr.
The origins of cholesterol research can be traced to prerevolutionary France. The discovery of cholesterol as a single substance, present in human gallstones, owes much to the scientists of l'Académie Française, including Lavoisier, who contributed so much to the emergence of chemistry as a modern scientific discipline. Since that time, cholesterol probably has been the most intensively scrutinized natural product of all time, and it has been the subject of Nobel Prizes for several who have studied its structure, biosynthesis, and regulation. The pace of research into cholesterol shows no sign of diminishing, and recent discoveries have led to the recognition that the regulation of cholesterol metabolism is intimately linked with that of other metabolic pathways. Details of these interactions are only just emerging, but it is becoming apparent that under some circumstances it is difficult to reconcile, in a conventional manner, changes in regulatory gene expression with corresponding changes in pathway carbon flux. The present review includes some of our studies on the roles of the transcription factors sterol regulatory element-binding protein, liver X-receptor alpha, and peroxisome proliferator activated receptor a in the coordination of cholesterol and fatty acid synthesis and describes how some of the results obtained can best be interpreted from a Metabolic Control Analysis perspective of the regulation of pathway carbon fluxes.


Perfusion balloon catheter.
An autoperfusion balloon catheter was developed to allow passive myocardial perfusion during balloon inflation, through a central lumen and multiple side holes in the shaft proximal and distal to the balloon. This report reviews preliminary experimental animal data and initial human clinical experience with this device. In our first study with this device, the duration of inflation in dogs was compared with the maximal duration of inflation using a standard angioplasty catheter. Coronary arteriography was performed to demonstrate distal coronary blood flow through the perfusion balloon catheter. Electrocardiographic recordings and repeated left ventriculograms were performed to detect evidence of ischemia during standard and perfusion and balloon catheter inflations. The average inflation time was 3 +/- 1 minute for the standard catheter and 37 +/- 10 minutes for the perfusion catheter. Each dog had evidence of severe myocardial ischemia during standard inflation, yet none of the animals had ST-segment elevation, ventricular arrhythmia or wall motion abnormality during dilatation with the perfusion catheter. In a second experiment, the effect of prolonged balloon inflations (30 minutes) on intimal hyperplasia was evaluated in the rabbit model. Results of this study showed reduction of intimal and medial hyperplasia after 4 weeks in iliac arteries in rabbits treated with prolonged inflations compared with the contralateral vessel in rabbits treated with standard angioplasty. Initial clinical results from patients treated with this new catheter are presented. The availability of an effective autoperfusion catheter should allow for testing the hypothesis that prolonged inflations could alter the acute angioplasty success rate and long-term restenosis rate.


The complete mitochondrial genome sequence of Garrulax poecilorhynchus (Aves, Passeriformes, Timaliidae).
The entire mitochondrial genome of Garrulax poecilorhynchus consists of 17 814 bp and containe 13 protein-coding genes, 22 tRNA genes, two rRNA genes, and two control regions. The nucleotide composition of the mitogenome of G. poecilorhynchus is A = 5342 (29.99%), T = 4314 (24.22%), G = 2480 (13.92%), and C = 5678 (31.87%). The genome has an overall A + T content of 54.21%, which has a similar value among known genus Garrulax mitogenomes. All the tRNA genes display a typical clover-leaf structure. Garrulax poecilorhynchus share the closest relationship with other two species, G. perspicillatus and G. sannio. These data could serve to enrich the resource of genus Garrulax in systematic, population genetic, and evolutionary biological studies.


Dynamic investigation of nutrient consumption and injection strategy in microbial enhanced oil recovery (MEOR) by means of large-scale experiments.
Microbial enhanced oil recovery (MEOR) depends on the in situ microbial activity to release trapped oil in reservoirs. In practice, undesired consumption is a universal phenomenon but cannot be observed effectively in small-scale physical simulations due to the scale effect. The present paper investigates the dynamics of oil recovery, biomass and nutrient consumption in a series of flooding experiments in a dedicated large-scale sand-pack column. First, control experiments of nutrient transportation with and without microbial consumption were conducted, which characterized the nutrient loss during transportation. Then, a standard microbial flooding experiment was performed recovering additional oil (4.9 % Original Oil in Place, OOIP), during which microbial activity mostly occurred upstream, where oil saturation declined earlier and steeper than downstream in the column. Subsequently, more oil remained downstream due to nutrient shortage. Finally, further research was conducted to enhance the ultimate recovery by optimizing the injection strategy. An extra 3.5 % OOIP was recovered when the nutrients were injected in the middle of the column, and another additional 11.9 % OOIP were recovered by altering the timing of nutrient injection.


Noninvasive tumor imaging with high-frequency ultrasound and microPET in small animals.
In this study, we used a micro-ultrasound (microUS) system that we developed in-house as an alternative method for tumor growth calipers. In addition, microUS was combined with small-animal positron-emission tomography (microPET) for tumor metastatic assessment. MicroUS provides anatomical information that can be used for tumor volume measurements while microPET is a functional imaging method with positron-emitting radiophamaceuticals, such as 18F-labeled deoxyglucose, [18F]FDG. In this study, microUS and microPET were performed in a mouse tumor longitudinal study (2-8 weeks), both with 3D tumor segmentation and volume measurements. Compared with vernier calipers, microPET generally overestimated tumor volumes during weeks 2-4 due to its inadequate spatial resolution. During weeks 5-8, standard deviations of microPET results were large due to tumor hypoxia or necrosis. On the contrary, microUS tumor volume measurements were more reliable as they were less affected by these factors. Nonetheless, microUS is not able to provide functional information similar to that provided by microPET. Therefore, microUS and microPET are complementary to each other as microUS has superior spatial resolution and microPET provides functional information, such as hypoxia or necrosis in the progression of the tumor. With image registration and fusion, the combination can be a valuable tool for cancer research.


Genetic interaction of PICALM and APOE is associated with brain atrophy and cognitive impairment in Alzheimer's disease.
Evidence has emerged indicating that the ε4 allele of APOE and PICALM interact in conferring risk of Alzheimer's disease (AD). The biologic basis of this interaction is unclear, but it is likely to have phenotypic relevance and contribute to the structural and clinical heterogeneity of AD. The aim of this study was to investigate interaction effects of the APOE ε4 allele and the alleles at the single-nucleotide polymorphism rs3851179 located in the PICALM locus. We analyzed brain volumes and cognitive phenotypes of 165 patients with early AD dementia. There was a synergistic adverse effect of homozygosity for the PICALM risk allele G in rs3851179 and APOE ε4 on volume in prefrontal and performance on the Trail Making Test A, which is sensitive to processing speed and working memory function. The data suggest a neural mechanism for APOE-PICALM interactions in patients with manifest AD and indicate that the PICALM genotype modulates both brain atrophy and cognitive performance in APOE ε4 carriers.


Insights and controversies into the role of the key apicomplexan invasion ligand, Apical Membrane Antigen 1.
Apicomplexan parasites are obligate intracellular pathogens that cause a host of human and animal diseases. These parasites have developed a universal mechanism of invasion involving formation of a 'moving junction' that provides a stable anchoring point through which the parasite invades host cells. The composition of the moving junction, particularly the presence of the protein Apical Membrane Antigen 1 (AMA1), has recently been the subject of some controversy. In this commentary we review findings that led to the current model of the moving junction complex and dissect the major conflicts to determine whether a substantial reassessment of the role of AMA1 is justified.


Recognition and management of Lyme disease.
Lyme disease, the most common tick-borne illness in the United States, has an annual incidence of 0.5 percent in endemic areas. It most commonly occurs in the Northeast and upper Midwest, in areas that encourage and harbor the deer tick. The tick transmits an infection of the spirochete Borrelia burgdorferi that typically manifests as a localized skin lesion, erythema migrans. Rarely, Lyme disease manifests as localized arthritis, heart block or disease of the nervous system. Lyme disease is a clinical diagnosis, and laboratory tests should only be used to clarify diagnostic issues. The current standard for laboratory diagnosis includes a two-step approach using an initial immunoassay with a confirmatory Western blot. Treatment includes 10 to 21 days of oral doxycycline in nonpregnant adults or a similar course of amoxicillin in children or pregnant women. Overdiagnosis and overtreatment of Lyme disease have become common.