[The expression of Plakoglobin in residual cancer after neoadjuvant chemotherapy for breast cancer and its prognostic impact on patients].

Objective: To investigate the relationship between the expression levels of Plakoglobin protein in residual lesions after neoadjuvant chemotherapy (NAC) and the prognosis of breast cancer patients. Methods: Clinical and pathological data from 174 breast cancer patients who underwent surgery after receiving NAC at the Cancer Hospital of Chinese Academy of Medical Sciences from January 2009 to December 2017 were collected. The expression level of Plakoglobin in residual cancer lesions was evaluated by immunohistochemistry. The correlation between Plakoglobin expression level and clinicopathological features was analyzed. Survival analysis was performed using the Kaplan-Meier method, and Cox proportional hazard regression models were used for factor analysis. Results: Among the 174 patients, 140 had low expression of Plakoglobin, and 34 had high expression. The median disease-free survival (DFS) and overall survival (OS) in the Plakoglobin low expression group were 59.46 and 71.68 months, respectively, both of which were higher than those in the high expression group (36.58 and 47.26 months, respectively, both P<0.05). Univariate analysis showed that Plakoglobin expression, pathological N stage, lymphovascular invasion status, histological grade, Ki-67, and molecular subtypes were associated with OS (all P<0.05), while pathological N stage, histological grade, and Ki-67 were associated with DFS (all P<0.05). Multivariate analysis revealed that Plakoglobin expression (HR=2.438, 95% CI: 1.256-4.735, P=0.008) was an independent predictor for OS, and Ki-67 (HR=2.228, 95% CI: 1.316-3.773, P=0.003) was an independent predictor for DFS. Conclusion: In breast cancer patients with residual lesions after NAC, those with low Plakoglobin expression have relatively longer OS and Plakoglobin is an independent prognostic factor for OS.

Quantifying Sarcopenia Reference Values Using Lumbar and Thoracic Muscle Areas in a Healthy Population.

BACKGROUND: Sarcopenia is defined as the loss of skeletal muscle mass and function associated with aging. Muscle mass can be reliably and accurately quantified using clinical CT scans but reference measurements are lacking, particularly in healthy US populations. METHODS: Two-phase CT scans from healthy kidney donors (age 18-40) at the University of Michigan between 1999-2010 were utilized. Muscle mass was quantified using two thoracic and two lumbar muscle cross-sectional area (CSA) measures. Indexed measurements were computed as area divided by height-squared. Paired analyses of non-contrast and contrast phases and different Hounsfield Unit (HU) ranges for muscle were conducted to determine their effect on CSA muscle measures. We report the means, standard deviations, and 2SD sarcopenia cutoffs from this population. RESULTS: Healthy population CSA (cm2) cutoffs for N=604 males/females respectively were: 34.7/20.9 (T12 Dorsal Muscle), 91.5/55.9 (T12 Skeletal Muscle), 141.7/91.2 (L3 Skeletal Muscle), 23.5/14.3 (L4 Total Psoas Area), and 23.4/14.3 (L4 Psoas Muscle Area). Height-indexed CSA (cm2/m2) cutoffs for males/females respectively were: 10.9/7.8 (T12 Dorsal Muscle), 28.7/20.6 (T12 Skeletal Muscle), 44.6/34.0 (L3 Skeletal Muscle), 7.5/5.2 (L4 Total Psoas Area), and 7.4/5.2 (L4 Psoas Muscle Area). We confirmed that a mask of -29 to 150 HU is optimal and shows no significant difference between contrast-enhanced and non-contrast CT scan CSA measurements. CONCLUSIONS: We quantified reference values for lumbar and thoracic muscle CSA measures in a healthy US population. We defined the effect of IV contrast and different HU ranges for muscle. Combined, these results facilitate the extraction of clinically valuable data from the large numbers of existing scans performed for medical indications.

Analytical compensation of axisymmetric equilibrium fluxes picked up by locked mode detectors in tokamaks.

In the detection of locked modes using saddle loops, the problem of how to remove the axisymmetric equilibrium flux picked up by the loops has still to be solved. The problem becomes more difficult when there are conductive structures located near the saddle loops. In this paper, we present an analytical model based on lumped eddy current circuits and use it to interpret the measured equilibrium flux and the corresponding eddy current fluxes. Using this model, precise compensation for fluxes induced by the horizontal field coils and the toroidal field coils, with relative errors of less than 1%, has been realized for the saddle loops in the Joint Texas Experimental Tokamak. This paper also presents a new method to compensate for the detection of equilibrium flux by the locked mode detector.

Measurement of 2∕1 intrinsic error field of Joint TEXT tokamak.

The amplitude and spatial phase of the intrinsic error field of Joint TEXT (J-TEXT) tokamak were measured by scanning the spatial phase of an externally exerted resonant magnetic perturbation and fitting the mode locking thresholds. For a typical plasma with current of 180 kA, the amplitude of the 2∕1 component of the error field at the plasma edge is measured to be 0.31 G, which is about 1.8 × 10(-5) relative to the base toroidal field. The measured spatial phase is about 317° in the specified coordinate system (r, θ, ϕ) of J-TEXT tokamak. An analytical model based on the dynamics of rotating island is developed to verify the measured phase.

A rare skin presentation of Penicillium marneffei infection in an AIDS patient.

Penicillium marneffei is an opportunistic fungal pathogen in HIV disease. We report the case of a patient with AIDS who presented with general weakness and generalized skin rashes. No specific allergic history or recent medication were reported. The skin lesions disappeared after adequate antifungal therapy. A blood culture obtained from the patient confirmed the presence of P. marneffei, infection which is characterized by cutaneous umbilicated lesions in AIDS patients. We report this case on account of the unusual skin presentation.

Endoscopic resection of hypothalamic hamartomas for refractory symptomatic epilepsy.

BACKGROUND: Hypothalamic hamartomas (HHs), rare developmental abnormalities of the inferior hypothalamus, often cause refractory, symptomatic, mixed epilepsy, including gelastic seizures. We present 37 patients with HH who underwent transcortical transventricular endoscopic resection. METHODS: Between October 2003 and April 2005, 42 consecutive patients with refractory epilepsy who underwent endoscopic resection of HH were studied prospectively. The endoscope was held by an articulated pneumatic arm and tracked with a frameless stereotactic neuronavigation system. Data collection and follow-up were performed by personal interview. Five patients were excluded. The remaining 37 patients (22 males, 15 females; median age 11.8 years; range 8 months to 55 years) had frequent and usually multiple types of seizures. RESULTS: Postoperative MRI confirmed 100% resection of the HH from the hypothalamus in 12 patients. At last follow-up (median 21 months; range 13-28 months), 18 (48.6%) patients were seizure free. Seizures were reduced more than 90% in 26 patients (70.3%) and by 50% to 90% in 8 patients (21.6%). Overall, the mean postoperative stay was shorter in the endoscopic patients compared with our previously reported patients who underwent transcallosal resection (mean 4.1 days vs 7.7 days, respectively; p = 0.0006). The main complications were permanent short-term memory loss in 3 patients and small thalamic infarcts in 11 patients (asymptomatic in 9). CONCLUSIONS: Endoscopic resection of hypothalamic hamartoma (HH) is a safe and effective treatment for seizures. Its efficacy seems to be comparable to that of transcallosal resection of HH, but postoperative recovery time is significantly shorter.

Listerial meningitis in a patient with undiagnosed acquired immunodeficiency syndrome: ampicillin should be added to the empirical antibiotic coverage.

Meningitis is an important differential diagnosis in patients with fever, headache, and/or altered consciousness in the emergency department (ED). With human immunodeficiency virus (HIV) infection becoming increasingly common, patients with acquired immunodeficiency syndrome (AIDS) need to be recognised promptly to facilitate the choice of appropriate antibiotic therapy for potential opportunistic infections. Physicians should be able to recognise a patient with undiagnosed AIDS who presents to the ED and perform further confirmational tests without violating the rights of the patient. Additional tests focusing on discovering potential opportunistic pathogens should be performed. Ampicillin should be added to the empirical regimen for the coverage of Listeria meningocerebritis, which should be considered in all potentially immunocompromised hosts with suggestive clinical presentations. Failure to recognise patients with AIDS and provide antibiotics active against L monocytogenes in such hosts may lead to a catastrophic outcome.

Optical mapping of ventricular defibrillation in isolated swine right ventricles: demonstration of a postshock isoelectric window after near-threshold defibrillation shocks.

BACKGROUND: Investigators who studied ventricular defibrillation by use of optical mapping techniques failed to observe an initial defibrillation event (isoelectric window or quiescent period) shown by electrode mapping studies. This discrepancy has important implications for the mechanisms of defibrillation. The purpose of the present study was to demonstrate an optical equivalent of an isoelectric window after a near-threshold defibrillation shock. Methods and Results-- We studied 10 isolated, perfused swine right ventricles. Upper limit of vulnerability was determined by shocks on T waves. A 50% probability of successful defibrillation (DFT50) was determined with an up-down algorithm. Immediately after unsuccessful defibrillation shock, new wavefronts were generated. When the shock strength was low, immediate reinitiation of reentry and ventricular fibrillation might occur without a postshock isoelectric window. However, if the shock strength was within 50 V of DFT50 (near-threshold), a synchronized activation occurred, followed by organized repolarization that ended 64+/-18 ms after shock. After a period of quiescence (18+/-24 ms), activation recurred 83+/-33 ms after shock and reinitiated ventricular fibrillation. Similar patterns of activation, including a quiescent period, were observed after shock was applied on the T wave of the paced beat that induced ventricular fibrillation. Upper limit of vulnerability correlated well with DFT50. CONCLUSIONS: In isolated swine right ventricles, an optical equivalent of an isoelectric window exists after near-threshold defibrillation shocks. These findings support the idea that a near-threshold defibrillation shock terminates all activation wavefronts but fails to halt ventricular fibrillation because the same shock reinitiates ventricular fibrillation after an isoelectric window.

Patterns of wave break during ventricular fibrillation in isolated swine right ventricle.

Several different patterns of wave break have been described by mapping of the tissue surface during fibrillation. However, it is not clear whether these surface patterns are caused by multiple distinct mechanisms or by a single mechanism. To determine the mechanism by which wave breaks are generated during ventricular fibrillation, we conducted optical mapping studies and single cell transmembrane potential recording in six isolated swine right ventricles (RV). Among 763 episodes of wave break (0.75 times x s(-1) x cm(-2)), optical maps showed three patterns: 80% due to a wave front encountering the refractory wave back of another wave, 11.5% due to wave fronts passing perpendicular to each other, and 8.5% due to a new (target) wave arising just beyond the refractory tail of a previous wave. Computer simulations of scroll waves in three-dimensional tissue showed that these surface patterns could be attributed to two fundamental mechanisms: head-tail interactions and filament break. We conclude that during sustained ventricular fibrillation in swine RV, surface patterns of wave break are produced by two fundamental mechanisms: head-tail interaction between waves and filament break.

Comparing cardiac action potentials recorded with metal and glass microelectrodes.

Machine-pulled high-impedance glass capillary microelectrode is standard for transmembrane potential (TMP) recordings. However, it is fragile and difficult to impale, especially in beating myocardial tissues. We hypothesize that a high-impedance pure iridium metal electrode can be used as an alternative to the glass microelectrode for TMP recording. The TMPs were simultaneously recorded from isolated perfused swine right ventricles with a metal microelectrode and a standard glass microelectrode during pacing and during ventricular fibrillation. The basic morphology of TMP recorded with these electrodes was comparable. The action potential duration (APD) at 90% repolarization was 241 +/- 29 ms for the metal microelectrode and 236 +/- 31 ms for the glass microelectrode with a good correlation (r = 0.99, P < 0.0001). The maximum slope value of the APD restitution curves during pacing was also significantly correlated. One metal microelectrode and >20 glass microelectrodes were needed per study. We conclude that, in isolated perfused swine right ventricles, the TMP recorded by the metal microelectrode is comparable with that recorded by the glass microelectrode. Because the metal microelectrode is more durable than the glass microelectrode, it can serve as an alternative for APD recording and for restitution analyses.

Control of dengue vectors in Singapore.

Singapore has a well-established system for the surveillance, research and control of Aedes aegypti and Aedes albopictus. Control of these vectors comes under the jurisdiction of the Environmental Public Health Division of the Ministry of the Environment. The strategy for Aedes control is an integrated approach incorporating case detection, source reduction, health education and law enforcement. This is done through the Quarantine & Epidemiology Department (dengue surveillance and research), Vector Control & Research Department (Aedes surveillance, control and research), Environmental Health Department (environmental sanitation and hygiene) and Public Education Department (health education on dengue prevention and control). Despite its success in reducing the Aedes population to a house index of around 1%, the incidence of dengue fever/dengue haemorrhagic fever has increased sharply during the last 5 years. The Ministry realises that the dengue problem can only be tackled on a regional basis and it is with this objective in mind that the Institute of Environmental Epidemiology has been formed to collaborate with other international agencies in operational research and training projects.

Multiple genes provide the basis for antifreeze protein diversity and dosage in the ocean pout, Macrozoarces americanus.

The ocean pout (Macrozoarces americanus) produces a set of antifreeze proteins that depresses the freezing point of its blood by binding to, and inhibiting the growth of, ice crystals. The amino acid sequences of all the major components of the ocean pout antifreeze proteins, including the immunologically distinct QAE component, have been derived by Edman degradation. In addition, sequences of several minor components were deduced from DNA sequencing of cDNA and genomic clones. Fifty percent of the amino acids are perfectly conserved in all these proteins as well as in two homologous sequences from the distantly related wolffish. Several of the conserved residues are threonines and asparagines, amino acids that have been implicated in ice binding in the structurally unrelated antifreeze protein of the righteye flounders. Aside from minor differences in post-translational modifications, heterogeneity in antifreeze protein components stems from amino acid differences encoded by multiple genes. Based on genomic Southern blots and library cloning statistics there are 150 copies of the 0.7-kilobase-long antifreeze protein gene in the Newfoundland ocean pout, the majority of which are closely linked but irregularly spaced. A more southerly population of ocean pout from New Brunswick in which the circulating antifreeze protein levels are considerably lower has approximately one-quater as many antifreeze protein genes. Thus, there appears to be a correlation between gene dosage and antifreeze protein levels, and hence the ability to survive in ice-laden seawater. Southern blot comparison of the two populations indicates that the differences in gene dosage were not generated by a simple set of deletions/duplications. They are more likely to be the result of differential amplification.

Biosynthesis of antifreeze polypeptides in the winter flounder. Characterization and seasonal occurrence of precursor polypeptides.

The precursor proteins for winter flounder antifreeze polypeptide (AFP) were isolated from liver using gel filtration chromatography and reverse-phase high-performance liquid chromatography. Two major pro-antifreezes (Mr 5000), corresponding to the precursors for AFP-6 and AFP-8, were characterized by amino acid analyses and automated Edman degradation. These precursors showed significant antifreeze activity. The pro-antifreezes were synthesized in the liver seasonally as demonstrated by immunoblotting and in vitro liver incorporation studies. No mature AFP were detected in liver, thus indicating that the processing of pro-antifreezes, including amidation of the C-termini, occurred mainly in the serum. The function(s) of the prosequences, if any, remain unclear.

Molecular cloning and sequencing of salmon gonadotropin beta subunit.

Gonadotropin (GTH) was purified from the pituitaries of the Pacific chinook salmon using a combination of stepwise ethanol precipitation and concanavalin-A affinity chromatography. The alpha and beta subunits were dissociated and fractionated by C-18 reverse-phase high-performance liquid chromatography with a 0.1% trifluoroacetic acid/acetonitrile gradient. An enriched cDNA library was screened for the beta-GTH gene(s) using two synthetic oligonucleotides based on partial protein data. A positive, full-size clone (E3) was identified and sequenced. It contains 657 base pairs and codes for a 142-amino-acid precursor protein. The mature salmon beta-GTH (119 amino acids) is structurally homologous to human luteinizing hormone and chorionic gonadotropin. The effect of testosterone implantation on pituitary GTH and beta-GTH mRNA was examined with radioimmunoassay and Northern blot analysis. There was a corresponding increase in both the pituitary GTH and mRNA levels.

Ion-induced DNA structure change in nucleosomes.

Physical methods have been used to study calcium binding to the nucleosome core particle. Equilibrium dialysis of Ca2+ and spectroscopic analysis of a Ca2+ analogue show that the ion binds tightly to the particles, resulting in a significant change of DNA circular dichroism. This suggests that base stacking may be altered as a result of Ca2+ binding. In the presence of Ca2+, the absorbance and fluorescence properties of methylene blue (MB), a DNA-specific intercalator, confirm that the dye binds tightly to nucleosomes by intercalation. However, secondary changes occur which suggest that the MB binding site is altered as a result of Ca2+ binding. Triplet state anisotropy decay and triplet lifetime quenching both show that in the Ca2+-nucleosome complex, methylene blue is capable of wobbling over a substantial angular range at its binding site. To explain these data, it is proposed that Ca2+ binding to nucleosomes causes DNA to fold by means of a series of sharp bends (kinks). The properties of bound MB are best explained if it is presumed that the intercalator binds tightly to such kinked sites in the nucleosome. On the basis of these observations, we discuss the possibility that multivalent ion concentration in the nucleus is high enough that the smooth to kinked helix equilibrium may be near to its midpoint. Near such a midpoint, the secondary structure of DNA in the nucleosome might prove to be sensitive to effector molecule binding and to site-specific variation of DNA or histone composition within genes.

Structures of shorthorn sculpin antifreeze polypeptides.

The amino acid sequences of the two major antifreeze polypeptides (AFP) from the shorthorn sculpin have been determined using an automatic protein sequencer and enzymic digestion. These two polypeptides, SS-3 and SS-8, consist of 33 and 45 amino acid residues respectively. The N-terminal methionyl residue is blocked in both the polypeptides. When aligned for maximum structural similarity these two AFP are 80% homologous, and there appears a deletion of 12 amino acid residues at the N-terminal portion of SS-3. Like the winter flounder AFP, both the sculpin AFP also contain the 11-amino-acid repeat sequences. The secondary structure of the sculpin AFP is mainly alpha-helical as deduced from circular dichroic spectral data. The helical content of SS-8 is high (73%), while that of SS-3 is moderate (about 45%). The latter exhibits a relatively weak antifreeze activity. Removal of the blocked N-terminal residue in SS-8 did not alter the helical content significantly but did reduce the antifreeze activity. Helical contents of proteolytically generated fragments of AFP are much lower, and they are devoid of activity. The alpha-helix in the SS-8 component is seen to be amphiphilic in character. The relevance of this feature to the mechanism of the antifreeze action is briefly discussed.