Noninvasively determined muscle oxygen saturation is an early indicator of central hypovolemia in humans.

Ten healthy human volunteers were subjected to progressive lower body negative pressure (LBNP) to the onset of cardiovascular collapse to compare the response of noninvasively determined skin and fat corrected deep muscle oxygen saturation (SmO2) and pH to standard hemodynamic parameters for early detection of imminent hemodynamic instability. Muscle SmO2 and pH were determined with a novel near infrared spectroscopic (NIRS) technique. Heart rate (HR) was measured continuously via ECG, and arterial blood pressure (BP) and stroke volume (SV) were obtained noninvasively via Finometer and impedance cardiography on a beat-to-beat basis. SmO2 and SV were significantly decreased during the first LBNP level (-15 mmHg), whereas HR and BP were late indicators of impending cardiovascular collapse. SmO2 declined in parallel with SV and inversely with total peripheral resistance, suggesting, in this model, that SmO2 is an early indicator of a reduction in oxygen delivery through vasoconstriction. Muscle pH decreased later, suggesting an imbalance between delivery and demand. Spectroscopic determination of SmO2 is noninvasive and continuous, providing an early indication of impending cardiovascular collapse resulting from progressive reduction in central blood volume.     

Detection of altered N-glycan profiles in whole serum from rheumatoid arthritis patients

Altered N-glycosylation occurs in many diseases. In rheumatoid arthritis (RA), for example, reduction in galactose residues in IgG and an increase in fucose residues in alpha1-acid glycoprotein have been observed. To further analyse N-glycans in disease, we show N-glycan profiling from whole serum employing reversed phase high performance liquid chromatography/negative-ion mode by sonic spray ionization ion trap mass spectrometry with pyridylamination. Profiles from female 15 RA patients and 18 aged-matched healthy women were compared. The most significant change seen in RA was decreased levels of mono-galactosyl bi-antennary N-glycans, in agreement with the previous reports regarding IgG. We also show previously unreported differences between isomers and increased tri-antennary oligosaccharides. These results indicate that LC-MS analysis of whole serum N-glycans can identify N-glycan alterations in RA and that this is a promising method both for studies of RA mechanisms and diagnosis.     

Secreted ERBB3 isoforms are serum markers for early hepatoma in patients with chronic hepatitis and cirrhosis

Most hepatocellular carcinoma (HCC) is generated from chronic hepatitis and cirrhosis. To discover new markers for early HCC in patients with chronic hepatitis and cirrhosis, we initiated our search in the interstitial fluid of tumor (TIF) via differential gel electrophoresis and antibody arrays and identified secreted ERBB3 isoforms (sERBB3). The performance of serum sERBB3 in diagnosis of HCC was analyzed using receiver operating characteristic curves (ROC). The serum sERBB3 level was significantly higher in HCC than in cirrhosis (p < 0.001) and chronic hepatitis (p < 0.001). The accuracy of serum sERBB3 in detection of HCC was further validated in two independent sets of patients. In discrimination of early HCC from chronic hepatitis or cirrhosis, serum sERBB3 had a better performance than alpha-fetoprotein (AFP) (areas under ROC [AUC]: sERBB3 vs AFP = 93.1 vs 81.0% from chronic hepatitis and 70.9 vs 62.7% from cirrhosis). Combination of sERBB3 and AFP further improved the accuracy in detection of early HCC from chronic hepatitis (AUC = 97.1%) or cirrhosis (AUC = 77.5%). Higher serum sERBB3 levels were associated with portal-vein invasion and extrahepatic metastasis of HCC (p = 0.017). Therefore, sERBB3 are serum markers for early HCC in patients with chronic hepatitis and cirrhosis.     

ACPA fine-specificity profiles in early rheumatoid arthritis patients do not correlate with clinical features at baseline or with disease progression

Introduction

Autoantibodies against citrullinated peptides/proteins (ACPA) are found in approximately 75% of the sera of patients with rheumatoid arthritis (RA). The RA-specific ACPA are frequently present prior to disease onset and their presence associates with a more erosive disease course. ACPA can therefore be used to aid the diagnosis and prognosis of RA. Recently, it became clear that ACPA are very heterogeneous, both in an individual patient and among different patients. The aim of this study was to investigate whether clinically meaningful ACPA profiles exist in early RA patients.

Methods

Twenty citrullinated peptides and the corresponding non-citrullinated control peptides were immobilized on microarray sensor chips. Sera from 374 early arthritis patients were analyzed by surface plasmon resonance imaging (iSPR) of biomolecular interactions on the sensor chip.

Results

Cluster analysis of the reactivities with the citrullinated peptides, after subtraction of the reactivities with the corresponding control peptides confirmed the heterogeneity of the ACPA response in RA and revealed 12 distinct ACPA profiles. The association of the 5 most frequent profiles with clinical features at diagnosis and during the disease course was examined, showing no statistically significant associations.

Conclusions

Compared to the detection of ACPA in RA sera by CCP-based assays, ACPA profiling in early arthritis patients did not reveal associations with disease activity and progression scores.     

Correction of defective early tyrosinase processing by bafilomycin A1 and monensin in pink-eyed dilution melanocytes

Mutations in the human P gene result in oculocutaneous albinism type 2, the most common form of albinism. Mouse melan-p1 melanocytes, cultured from mice null at the homologous pink-eyed dilution (p) locus, exhibit defective melanin production. A variety of compounds including tyrosine, NH4Cl, bafilomycin A1, concanamycin, monensin, and nigericin are capable of restoring melanin synthesis in these cells. In the current study, we investigated the subcellular effects of bafilomycin A1 and monensin treatment of melan-p1 cells. Both agents play two roles in the processing of tyrosinase (Tyr) in melan-p1 cells. First, combined glycosidase digestion and immunoblotting analysis showed that these agents reduce levels of Tyr retained in the endoplasmic reticulum (ER) and facilitate the release of Tyr from the ER to the Golgi. Secondly, treatment with these compounds resulted in the stabilization of Tyr. Surprisingly, induction of melanin synthesis corresponds more closely with diminution of ER-retained Tyr, rather than the absolute amount of Tyr. Our results suggest that bafilomycin A1 and monensin induce melanin synthesis in melan-p1 cells mainly by facilitating Tyr processing from the ER to the Golgi by increasing the pH in either the ER or the ER-Golgi intermediate compartment.     

Differences between the metabolic profiles of decompensated and compensated cirrhosis patients with Hepatitis B virus infections under high-performance liquid chromatography-mass spectrometry

To improve the grading and staging of liver cirrhosis among patients with HBV infection noninvasively, a high-performance liquid chromatography with mass spectrometry metabolomics method was used to investigate the potential metabolic biomarkers in the serum of patients with different degrees of hepatic cirrhosis. The results demonstrate that lysophosphatidyl choline (LPC) from positive electrospray ionization (ESI) mode, and fatty acids and bile acids from negative ESI mode play important roles in distinguishing decompensated from compensated cirrhosis. A total of 21 differential metabolites were found from the two groups of patients. LPCs, fatty acids, and taurocholic acid (TCA) 3-sulfate decreased in patients with decompensated cirrhosis, whereas other bile acids increased significantly. The levels of TCA 3-sulfate, LPC 16:0, and LPC 18:0 were significantly correlated with the stages of the decompensated cirrhosis, and they may serve as potential biomarkers for the stage assessment of liver cirrhosis in patients with HBV infections.     

Reversal of migraine symptoms by Helicobacter pylori eradication therapy in patients with hepatitis-B-related liver cirrhosis

Helicobacter pylori infection might be associated with vascular diseases, such as primary Raynaud phenomenon and coronary heart diseases. The possible mechanism might be due to H. pylori antigens causing intermittent vasospasm of arterioles, which also played roles in the development of liver cirrhosis. Migraine, a functional vascular disease, was observed in many patients with cirrhosis in the clinic. This study aimed to assess the effects of H. pylori eradication on migraine symptoms in patients with hepatitis-B-virus-related cirrhosis. The results clearly showed that the intensity, duration, and frequency of attacks of migraine were significantly reduced in all the patients in whom H. pylori has been eradicated. Thus, the study pushed further insight into the mechanisms of migraine pathogenesis.     

Detection of autoantibodies to potentially amyloidogenic protein,gamma-synuclein,in the serum of patients with amyotrophic lateral sclerosis and cerebral circulatory disorders

In this study, we analyzed serum for the presence of antibodies to gamma-synuclein in patients with amyotrophic lateral sclerosis (ALS) compared to the control group of patients with other neurological diseases and healthy control donors. As a result, antibodies against gamma-synuclein are not an ALS-specific feature and have been identified in patients with ALS as well as in the control group patients. Patients with the impaired cerebral circulation showed increased incidence of autoantibodies to gamma-synuclein, yet the difference lacks statistical representativeness due to limited sample size.     

Detection of early Alzheimer's disease in MCI patients by the combination of MMSE and an episodic memory test

Background  

Mild cognitive impairment (MCI) is a heterogeneous clinical entity that comprises the prodromal phase of Alzheimer's disease (Pr-AD). New biomarkers are useful in detecting Pr-AD, but they are not universally available. We aimed to investigate baseline clinical and neuropsychological variables that might predict progression from MCI to AD dementia.