Tumor-associated proteases and inhibitors in gastric cancer: analysis of prognostic impact and individual risk protease patterns

OBJECTIVES: This study concerned the influence of 6 positions of the computer mouse on the work table on posture, muscular load, and perceived exertion during text editing. METHODS: An optoelectronic 3-dimensional motion analysis system was used to register the postures of 10 men and 10 women using video display units. Muscular load was also registered (with electromyography), as was perceived exertion (with rating scales). RESULTS: A neutral posture with a relaxed and supported arm showed the least perceived exertion, and the electromyographic results showed low activity in both trapezius muscles in this position. Short operators (all women) showed a numerically higher activity in the 4 examined muscles than the tall operators (all men, except 1). This finding could be related to lower muscle force among women and to anthropometric differences, which also influence biomechanic load moments. Narrow-shouldered operators (8 women and 1 man) and short operators worked with larger outward rotation and abduction of the shoulder in a position of the mouse lateral to the keyboard than the broad-shouldered (7 men and 2 women) and tall operators did. Arm support markedly reduced muscle load in the neck-shoulder region among the operators. CONCLUSIONS: The operators using video display units in this study preferred to use the mouse on a table in a close to relaxed, neutral posture of the arm in combination with arm support. Short and narrow-shouldered operators worked in more strenuous postures of the arm when the mouse was located lateral to the keyboard.     

Hibernation in ground squirrels induces state and species-specific tolerance to hypoxia and aglycemia: an in vitro study in hippocampal slices

This study investigated T-cell activation markers HLA-DR and CD69 in both naive (CD45RA+) and memory (CD45RA-) CD4+ as well as CD8+ T cells in peripheral blood of patients with autoimmune thyroiditis (AT, N = 28) or hyperthyroid untreated Graves' disease (GDH, N = 34) using three-color flow cytometry. It was demonstrated that patients with AT, but not those with GDH, expressed increased amounts of HLA-DR antigen compared to healthy subjects (HS, N = 26) on total CD4+ (AT: 14.1%; GDH: 11.3%; HS: 10.9%) and CD8+ cells (AT: 31.9%; GDH: 23.5%; HS: 19.4%) as well as on CD45RA- CD4+ cells (AT: 11.2%; GDH: 7.7%; HS: 7.9%). In GDH (+71%) and AT (+91%) only the proportion of HLA-DR+ CD45RA+ CD8+ cells was increased vs HS. Furthermore, euthyroid GD patients on methimazole (GDE, N = 22) displayed greater HLA-DR+ expression on total and CD45RA- cells within both CD4+ (+37 and 40%, respectively) and CD8+ cells (+47 and 93%, respectively) than GDH. In addition, total and CD45RA+ CD4+ and CD8+ cells were increased vs HS. In contrast, proportions of CD69 positive T cells were increased in AT and GDH on total CD4+ (+97 and 74%, respectively) and CD8+ (+95 and 68%, respectively) cells and all subsets thereof (except for CD45RA- cells in GDH), but normalized upon thyrostatic treatment. We conclude that patients with autoimmune thyroid disease harbor an almost twofold greater proportion vs HS of (a) HLA-DR+ CD45RA+ CD8+ T cells, and of (b) CD69 on total CD4+ and CD8+ cells, and an even more marked elevation on their CD45RA+ subset in AT and untreated GD. In addition, (c) thyrostatic treatment by methimazole in GD is accompanied by a further increase in circulating HLA-DR+ CD4+ and CD8+ cells and their CD45RA- subsets, but decreased CD69 expression. These data suggest association of HLA-DR expression with ongoing autoimmunity, while increased CD69 expression relates in part also to elevated thyroid hormone concentration in GDH.     

Erythropoietin production in rats with post-ischemic acute renal failure

To study the role of erythropoietin (Epo) in the pathogenesis of anemia in acute renal failure (ARF), organ Epo mRNA was measured by RNase protection assay in rats with ARF induced by a one hour-occlusion of the left renal artery. Hematocrit was significantly decreased two hours, 24 hours and one week after renal artery occlusion. A significant reduction in serum haptoglobin at two hours and an increase in serum LDH at 24 hours indicated that hemolysis was the likely cause of the initial fall in hematocrit. However, despite the reduced hematocrit, serum Epo concentrations were not significantly different from controls, suggesting that the anemia is maintained because of lack of an appropriate Epo response. Right renal Epo mRNA levels were not significantly different in all groups, but Epo mRNA levels in post-ischemic kidneys were 50 to 67% lower than in contralateral kidneys. However, Epo mRNA in the post-ischemic kidney was increased sixfold by acute hemorrhage, a rise comparable to the ninefold increase observed in contralateral kidneys. In ARF rats exposed to 7.5% O2 for four hours, right kidney Epo mRNA increased 200-fold over normoxic levels, to a value similar to sham-operated hypoxic controls. Epo mRNA in the post-ischemic kidney also increased 200-fold, to 50% of the level in the contralateral kidney. Hepatic Epo mRNA levels were elevated to comparable levels in both groups. In this ARF model, mild anemia is associated with relative Epo deficiency. In the post-ischemic kidney, a substantial capacity for Epo production is retained but the sensitivity of the Epo response to blood oxygen availability is significantly reduced.     

Oxytocin and milk removal are required for post-partum mammary-gland development

Following the introduction of a transvenous biatrial electrode configuration and a biphasic waveform for internal atrial defibrillation in patients in 1992, it was realized that the standard principles of efficient defibrillation derived from decades of ventricular defibrillation research would not provide painless atrial defibrillation in conscious patients. Over the last five years extensive experimental studies have addressed the risk of ventricular proarrhythmia from synchronized atrial shocks with reassuring results and the influence of the preceding R-R interval on the safety of atrial shocks has been established. Experimental atrial defibrillation research is now aimed at developing waveforms which are less painful and at exploring hybrid therapies including percutaneous right atrial compartmentalization by catheter ablation prior to atrial defibrillation and attempts at multisite pace-entrainment prior to and immediately following the delivery of perithreshold shocks.     

Identification of the regions of porcine VCP preventing its function in Saccharomyces cerevisiae

Photodynamic therapy with 5-aminolevulinic acid (ALA-PDT) is based on photosensitization by endogenous synthesis of protoporphyrin IX and its transient accumulation especially in malignant epithelially derived tissues. Recent studies have indicated that ALA-PDT is effective for the treatment of solar keratoses (SK), but there has been a lack of long-term clinical follow-up. The goal of the present study was to investigate the immediate and long-term effect of ALA-PDT on SK. Twenty-eight patients with a total of 251 SK were enrolled in the study. Standard treatment involved the topical application of 20% ALA, under occlusive and light-shielding dressing for 4 hours before exposure to UVA and/or different wave bands or wave band combinations of polychromatic visible light (full-spectrum visible light, and/or different wave bands of filtered visible light > 515, > 530, > 570, or > 610 nm) in one or two treatment sessions. The primary complete response rate of SK to ALA-PDT was 64% after one treatment, but 85% when the responses to a second treatment were included. Taken all treatments together, the complete response rate for lesions on face, scalp and neck was 93% for full-spectrum visible light, 96% for the combination of full-spectrum visible light and filtered light, 91% for different wave bands of filtered visible light, and 100% for the combination of long wave UVA and full-spectrum visible light, respectively. The complete response rate for lesions on forearms and hands was 51% for full-spectrum visible light and 33% for the combination of full-spectrum visible light and filtered light. The greater response rate for SK on the face, scalp, and neck was associated with a higher surface fluorescence and immediate response rate after ALA photosensitization at these sites (chi 2; p = 0.0001). However, due to the treatment protocol the mean light dose applied to lesions on the face, scalp and neck (50 J cm-2) was substantially higher than that for lesions on forearms and hands (35 J cm-2). In the long term follow-up of SK on face scalp and neck, the projected disease-free rate at 36 months after therapy was 71% for lesions treated with full-spectrum visible light versus 23% for lesions treated with different wave bands of filtered light (Log rank-Mantel Cox; p = 0.0001). These results indicate that treatment with full-spectrum visible light at higher light doses may be the most effective and promising form of light exposure in ALA-PDT of SK.     

The IgG binding site of human FcgammaRIIIB receptor involves CC' and FG loops of the membrane-proximal domain

Fc gamma receptors for the Fc part of IgG are the mediators for antibody effector functions. FcgammaRIII and FcgammaRII are low affinity receptors that, through the interaction with immune complexes, initiate a variety of immunological responses, such as phagocytosis, antibody-dependent cellular cytotoxicity, and release of inflammatory mediators. We set out to define the IgG binding site on human FcgammaRIII. We assumed that potential beta-turns in Ig-like domains are the most probable determinants for ligand binding, and chimeric FcgammaRIIIB/FcepsilonRI receptors as well as single residue mutants were constructed in these regions of FcgammaRIIIB. Substitution of four amino acids in the membrane-proximal domain (Gln126, Arg156, Lys162, Val164) resulted in decreased binding of human IgG1. Lys162 and Val164 were found also to be crucial for the interaction with the IgG-binding inhibitory monoclonal antibody 3G8. In a putative three-dimensional model constructed in this study, these residues map on the CC loop (Gln126), on F beta-sheet (Arg156), and on the FG loop (Lys162, Val164). Our data are consistent with the study about human FcgammaRII (Hulett, M. D., Witort, E., Brinkworth, R. I., McKenzie, I. F. C., and Hogarth, P. M. (1994) J. Biol. Chem. 269, 15287-15293), suggesting that common structural determinants, i.e. FG loop or the GFC surface of the membrane-proximal domain, can be involved in interactions with IgG by both low affinity receptor classes FcgammaRII and FcgammaRIII.     

Strong transient expression of the type I interferon-induced MxA protein in hepatitis A but not in acute hepatitis B and C

The human MxA protein is a new specific marker for type I interferon activity both in vitro and in vivo. In the study presented here, this interferon-induced marker, as well as the 2',5'-oligoadenylate synthetases, was measured in circulating mononuclear cells from 21 patients with acute hepatitis A, 20 patients with acute hepatitis B and 14 patients with acute hepatitis C for determination of the activation of the interferon system in these viral diseases. In acute hepatitis A a strong expression (10 of 10 patients) of the MxA protein and the 2',5'-oligoadenylate synthetase activity in peripheral-blood mononuclear cells was observed during the first 2 wk after onset of clinical symptoms. In this period the MxA protein concentrations reached levels similar to those measured in patients treated with up to 5 x 10(6) IU interferon-alpha three times a week. Beyond wk 3, in eight of eight patients with hepatitis A no increased MxA protein levels were found. In contrast, peripheral-blood mononuclear cells from patients with acute hepatitis B contained either no measurable MxA protein or only slightly higher levels of the MxA protein, as did those of most patients (12 of 14) with acute hepatitis C. The MxA protein levels of both hepatitis B and C patients were significantly lower (p < 0.05) than those found in hepatitis A patients. Furthermore, sera from 6 of 10 patients with hepatitis A, but none of 10 patients with acute hepatitis B and C, contained measurable MxA protein. This serum MxA protein may originate from interferon-exposed and subsequently damaged liver cells.(ABSTRACT TRUNCATED AT 250 WORDS)     

Minimum attack rate for measuring measles vaccine efficacy

BACKGROUND: For evaluating measles vaccine efficacy (VE) in the field, some investigators have suggested that an overall attack rate level of 5% or more in a randomly mixing population is sufficient to provide equal exposure to the viral agent in both vaccinated and unvaccinated groups. It is not clear, however, if this assumption is valid given the effect of herd immunity. METHODS: We created a computer simulation model based on the stochastic extension of the Reed-Frost model and tested for variation in bias in VE estimation due to herd immunity, based on runs of 200 trials. RESULTS: At higher levels of attack rate, the degree of herd immunity decreases, as does the percentage of trials with bias in VE estimation. The two main factors that affect the level of attack rate are the probability of adequate contact and the number of susceptibles. At a given level of attack rate, the number of susceptibles is positively associated with the percentage of biased trials in VE estimation. Since vaccination reduces the number of susceptibles, we also observe that when controlling for attack rate, higher vaccination coverage results in lower bias in VE estimation. CONCLUSION: The results show that the assumption of no bias when the attack rate is 5% or more becomes increasingly true when a large percentage of a randomly mixing population is immune.     

Water sorption characteristics of dried red peppers (Capsicum annum L.)

The water sorption isotherms of whole dried red pepper pods at 15, 25, 40°C were measured, and the results were used to test the applicability of the GAB equation, BET equation, and modified BET equation. the GAB, BET, and modified BET equations fitted the data well for water activities up to 0.93, 0.43, and 0.75, respectively. the monolayer values were found to range between 6 and 10 g H₂O per 100g solid, depending on temperature and the equation used for estimation. the excess heat of sorption as a function of moisture content was also determined.