Reduced volumes of the CA1 and CA4-dentate gyrus hippocampal subfields in systemic lupus erythematosus.

Introduction There is evidence for hippocampal dysfunctions in systemic lupus erythematosus (SLE), which may contribute to neuropsychiatric impairments. However, fine structural alterations of the hippocampus have not been investigated in SLE. Methods We measured the volume of hippocampal subfields in 18 SLE patients and 20 healthy control individuals matched for age, gender, and education. The MRI protocol included structural T1 volumes (Philips Achieva 3T scanner, magnetization-prepared rapid acquisition gradient echo (MPRAGE)). For image processing, we used the neuGRID platform and the longitudinal pipeline of FreeSurfer v6.0 with the "hipposubfields" flag. Results Patients with SLE showed reduced volumes of CA1 (Cornu Ammonis 1) and CA4-dentate gyrus subfields relative to the control individuals. Smaller CA1 volumes were associated with worse performance on the Addenbrooke's Cognitive Examination. Conclusions These preliminary results indicate a prominent vulnerability and functional relevance of the CA1 hippocampal subfield in SLE.

Isolation and characterization of eight microsatellite loci in the brook lamprey Lampetra planeri (Petromyzontiformes) using 454 sequence data.

Eight polymorphic microsatellite loci were developed for the brook lamprey Lampetra planeri through 454 sequencing and their usefulness was tested in 45 individuals of both L. planeri and the river lamprey Lampetra fluviatilis. The number of alleles per loci ranged between two and five; the Italian and Irish populations had a mean expected heterozygosity of 0·388 and 0·424 and a mean observed heterozygosity of 0·418 and 0·411, respectively.

Outcomes of adult orthotopic heart transplantation with extended allograft ischemic time.

BACKGROUND: Heart procurement for orthotopic heart transplant (OHT) is limited by the conventional 4 hours of ischemic time (IT). Based on a recent report from our center showing that extended IT from a young donor group is safe, we widened our geographical reach, resulting in almost 40% of our transplants having an IT > 4 hours. METHODS: We retrospectively reviewed records of adult patients who underwent OHT from January 2006 to December 2011. The primary outcome was survival, and secondary outcomes included resource utilization, end-organ dysfunction, and acute cellular rejection. Overall survival was analyzed using Kaplan-Meier curves and log-rank tests. Secondary outcomes were compared with a combination of parametric and nonparametric statistics. RESULTS: A total of 323 patients underwent OHT. There was a significant difference in overall survival between the standard and extended IT groups (85.7% vs 76.4%, P = .03). There were no significant differences between the groups for secondary outcomes except a higher incidence of liver dysfunction in the extended IT group (84.9% vs 73%, P = .01). Further analysis revealed that mortality remains similar if IT is below 4 hours and between 4 and 5 hours, but begins to climb after 5 hours, driving the difference between our standard and extended IT. CONCLUSIONS: Limited donor availability for OHT dictates alternative strategies to enlarge the donor pool. Although there is an overall increasing risk with extended IT beyond 4 hours, it may be possible to safely increase the threshold to at least 5 hours without compromising the outcomes.

Comparison of the Psoriatic Arthritis Quality of Life (PsAQoL) questionnaire, the functional status (HAQ) and utility (EQ-5D) measures in psoriatic arthritis: results from a cross-sectional survey.

OBJECTIVES: To compare the Psoriatic Arthritis Quality of Life (PsAQoL) instrument, the Health Assessment Questionnaire (HAQ) as a measure of functional status, and the generic health status (utility) measure the EuroQoL (EQ-5D) in terms of ability to assess disease severity in psoriatic arthritis (PsA). METHODS: The differences between known groups and correlations of the PsAQoL, the HAQ and the EQ-5D with clinical measures were analysed in a sample of 183 PsA patients. RESULTS: Different severities of PsA determined by known groups were distinguished well by all three questionnaires; more severe disease was associated with significantly worse values of the instruments. The correlations revealed a strong relationship between each of the measures, and with the patients' pain on the visual analogue scale (VAS), the patient global VAS, and the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), and a weak relationship with the disease duration and the Psoriasis Area Severity Index (PASI). The PsAQoL also correlated strongly with the 28-joint Disease Activity Score (DAS28). CONCLUSIONS: The PsAQoL, the HAQ, and the EQ-5D are able to distinguish well across levels of PsA severity.

Elevated levels of synovial fluid antibodies reactive with the small proteoglycans biglycan and decorin in patients with rheumatoid arthritis or other joint diseases.

OBJECTIVES: To determine whether patients with rheumatoid arthritis (RA) express humoral immunity to the small proteoglycans biglycan and decorin and to compare the response to that of patients suffering from other joint diseases. METHODS: Serum and synovial fluid IgG and IgM antibody levels were determined by enzyme-linked immunosorbent assay. Antibodies to biglycan and decorin as well as to other known and extensively investigated cartilage matrix components such as type II collagen, aggrecan and fibronectin were investigated. Patients suffering from RA, osteoarthritis (OA), psoriatic arthritis and other seronegative spondylarthropathies were included in the study. Correlation between antibody levels and clinical/laboratory parameters was determined. RESULTS: Patients with RA expressed an increased humoral immunity to biglycan, while patients with seronegative spondylarthropathies displayed elevated decorin-specific synovial antibody levels compared with OA patients. CONCLUSION: These results indicate a significantly higher immunity to small proteoglycans in RA and seronegative spondylarthropathies than in OA suggesting a possible involvement in the pathogenesis of inflammatory rheumatic diseases.

Interaction between nutrient supplies and aphid numbers on potato (2001-2002).

We set up our experiment on 11 potato varieties with 4 treatments and 4 replications in Hungary in 2001 and 2002. The aim of the experiment was to investigate the interaction between the nutrient supplies of potato and the change in the numbers of aphids feeding on the potato plant. In our experiment we sorted 4 nutrient levels according to the recommendations of soil analyses and variety holders. During the growing period we counted the numbers of aphids feeding on the potato leaves every week and controlled the virus infestation with ELISA-method after harvesting. Using the data we concluded that there is an interaction between the nutrient supplies of the potato plant and the numbers of aphids feeding on the leaves. The numbers of aphids on the plots with good nutrient supplies exceeded the numbers of aphids counted on the control plots. In 2001 and 2002 we counted 1150 and 1205 aphids per 100 plants on plots with nutrient supplies in the peak time of swarming compared to the control plot with numbers of 799 and 978. Beside nutrient supplies weather conditions influenced the numbers of aphids, too. Different temperature and rainfall conditions in both years affected the intense and progress of swarming. This can be the reason for the appearance of the first aphids (in the last week of April in 2001 and in the first week of May in 2002) and the time of swarming (15-18 June in 2001 and 28-31 May in 2002). Summer heat and hot days lowered the numbers of aphids. In 2002 following the heat in June and July the population escalated. After harvesting we confirmed our hypothesis from the tuber samples by ELISA-method: The virus infestation was higher on plots with intensive growing practice than the virus infestation on the control plots. In 2001 the rate of PLVRV infestation on Agria variety of the control plot yielded 18.7%. At the time of the 3rd treatment it increased to 37.2%. In 2002 the control had an infestation rate of 12.6% and 40.2% at the time of the 3rd treatment. In 2001 the rates of PVY infestation were 15.2% and 23.4% respectively and in 2002 they were 14.8% and 18.2% respectively. As the interaction between nutrient supplies, changes in the numbers of aphids and the virus infestation are not yet well known, further experiments are required.

Individual number change of Empoasca spp. cicadas species in potato.

We investigated the individual number change of Empoasca spp. cicadas species that are living in potatoes for 3 years. We applied the "100 plants" method for the determination for the individual number once per week. Based on the data determined that the settling of adult begins on the last days of May, and valid presence will be followed till the end of the breeding-season. The individual number was gradually increased during the settling, and reached the peak in 1990 on 23 July, in 2000 on 6 August and in 2001 on 22 July. We determined the individuals gathered during the collection. In the population of Empoasca spp. The E. solani Curtis and the E. decipiens Paoli played the dominant role. The E. vitis Göthe was also present with insignificant individual number. Beside the adults many larvae and nymphs were living on the potato which means that the Empoasca spp. Can reproduce also on the potato. At the time of peak individual number in 1999 1876 larvae, 344 nymphs and 400 adults were present on 100 plants, in 2000 (according to the previous order) 3340, 580, 1280, and in 2001 there were 954, 786 and 285. The rainfall in Hungary was disadvantageous in the investigated period, especially the year 2000. During the rain-free period the temperature was high and the relative humidity of the air was low. However, we could state that the increase of the cicada individual number was not restrained by the heat (30-35 degrees C) days. The decrease was in connection with the ageing of the plant stock.

Soluble interleukin-6 receptor in plasma and in lymphocyte culture supernatants of healthy individuals and patients with systemic lupus erythematosus and rheumatoid arthritis.

The soluble IL-6 receptor (sIL-6R) occurring in various body fluids of healthy persons and patients with various diseases is an agonist since its complex with IL-6 binds to gp130 making IL-6 receptor negative cells responsive for IL-6. The generation as well as the functional role of soluble IL-6 receptor is poorly understood. We measured the sIL-6R levels by ELISA sandwich technology in sera and in supernatants of lymphocyte cultures without and after incubations with dexamethasone. Our results indicate, that the sIL-6R levels in sera of patients with inactive systemic lupus erythematosus (SLE) and active rheumatoid arthritis (RA) were higher than those of the control group, active SLE and inactive RA. In vitro dexamethasone treatment stimulated generation of sIL-6R in both healthy persons and in active SLE, however it strongly suppressed sIL-6R in both RA groups. At mRNA level, we found that in SLE both the mRNA coding the cell-bound and an alternatively spliced variant corresponding to soluble IL-6R transcript increases, however the strong decrease of sIL6R protein in RA was not found at mRNA level.

Generation of 'truncated' interleukin-6 receptor (IL-6R) mRNA by alternative splicing; a possible source of soluble IL-6R.

Receptors for interleukin-6 (IL-6) occur in body fluids in soluble form, as well. This is an approx. 50 kDa protein with the ability to bind IL-6. The soluble IL-6 receptor (sIL-6R)/IL-6 complex can attach to membrane anchored gp130, a molecule associated with the signal transduction induced by IL-6 and by other related cytokines. Earlier we described the appearance of sIL-6R in various body fluids of autoimmune patients. In this study using reverse transcriptase polymerase chain reaction (RT-PCR) we isolated and characterised a truncated form of amplified cDNA reverse-transcribed from IL-6 receptor mRNA both from human hepatoma cell line HepG2 and mononuclear cells from inflammatory bowel disease (IBD) patients. Using digestion by Pvu II restriction endonuclease and direct nucleotide sequencing we conclude that alternative splicing is likely involved in generation of sIL-6R. Our further experiments suggest that IL-6 and recombinant sIL-6R themselves do not influence the alternative splicing of IL-6 receptor gene.

[Regulation of tetanus toxin-inhibited transmitter secretion in the neuromuscular junction in a calcium-free medium]. / Reguliatsiia ugnetennoi stolbniachnym toksinom sekretsii peredatchika v nervno-myshechnom soedinenii v beskal'tsievoi srede.

The effect of Ca2+ removal from the external medium on regulation of the release of the synaptic transmitter in the tetanus toxin (TT)-inhibited neuromuscular junctions was studied on a rat phrenicodiaphragmal preparation with the aid of the conventional microelectrode technique of recording synaptic activity. As the external concentration of calcium was decreased from 2 to 0 mM, the frequency of miniature end plate potentials remained unchanged in the preparations isolated 3 to 3.5 h after intramuscular injection of TT (10(5) MLD for mouse). TT considerably reduced activation of the transmitter release, caused in intact synapses by ouabain (0.1 mM) and repetitive stimulation of the diaphragmatic nerve (50 imp/s). The data obtained indicate that in the TT-inhibited motor nerve terminals, the level of the transmitter release does not depend on the external concentration of calcium and that TT damages some of the intracellular sources of calcium.

[Inherent morphofunctional effects of experimental procedures in studying the mechanism of transmitter release]. / Sobstvennye morfofunktsional'nye éffekty nekotorykh éksperimental'nykh protsedur pri izuchenii mekhanizma vydeleniia peredatchika.

Muscle detubulation with the aid of glycerin is widely used in studying synaptic transmission in the neuromuscular junction. In view of this fact, it was decided to examine its effects on structural and functional parameters of the neuromuscular junction of rat diaphragmal muscle. It was shown that the structure of the junction was on the whole preserved, although during glycerin treatment and for a certain period after glycerin washing off, some alterations were recorded (an increase in the volume of vesicles, a change in volume distribution of vesicles, and so forth). The interrelationship between axonal terminal and Schwann cells was altered. Addition of glycerin was found to provoke a transitory activation of the transmitter release, but later on no changes were seen.

[Changes in transmitter release processes in the rat neuromuscular junction as affected by calcium metabolic disorders]. / Perestroika protsessa sekretsii peredatchika v nervno-myshechnom soedinenii krysy v usloviiakh narusheniia kal'tsievogo obmena.

Spontaneous synaptic activity, miniature end plate potentials (MEPP), was recorded intracellularly in rat phrenic diaphragmatic preparations isolated 8-10 days after removal of the external lobes of the parathyroid glands, with the total blood serum calcium being decreased from 2.75 +/- 0.07 to 1.50 +/- 0.09 mM. The frequency of MEPP was high in both normocalcium (2 mM) and hypocalcium (1 mM) media and complete removal (1 mM EGTA) of Ca2+ from the preparation-washing solution. In the latter case one could observe two synaptical population with different levels of secretion activation. Besides, if judged from the distribution of MEPP amplitudes and the appearance of "spontaneous EPP", the pattern of transmitter exocytosis also experiences changes. It is assumed that under experimental endogenous hypocalcemia there develop functional restitutions in the axonal terminal, leading to the accumulation in them of the transmitter and (or) Ca2+.

[Effect of tetanus toxin on mechanisms by which calcium ions regulate transmitter secretion at the neuromuscular junction]. / Vliianie stolbniachnogo toksina na mekhanizmy reguliatsii ionami kal'tsiia sekretsii peredatchika v nervno-myshechnom soedinenii.

Phrenicodiaphragmal rat preparations were used to study the transmitter secretion by intracellular recording of end plate potentials (EPP) and miniature EPP (MEPP). In tetanus toxin-poisoned terminal, the regulatory effect of the external gradient of Ca2+ was abolished as evidenced by the fact that spontaneous secretion did not differ from that in calcium-free solution in health, as the external concentration of Ca2+ rose from 0 to 20 mM. Calcium ionophore A 23187 in intact terminals activated spontaneous release of the transmitter, but did not affect the poisoned terminal. Ouabain enhanced spontaneous secretion both in health and in poisoning. 4-Aminopyridine (4-AP) did not change the frequency of MEPP, while "giant" MEPPs that reflect spontaneous synchronization of the release of quants occurred both in health and in poisoning. 4-AP potentiated the reactivation effects of rhythmic stimulation of poisoned synapses, particularly with reference to the evoked release and led to the recovery of transmission. It is likely that tetanus toxin fixed by gangliosides of the presynaptic membrane prevents, in this particular case, the functioning of both endo- and exogenous ionophoroses that transport Ca2+ to the "active zones", without affecting their asynchronous supply from the intracellular depots.

[Changes in the ratio of quantum-vesicular parameters in the presence of disrupted synaptic transmitter secretion in the neuromuscular junctions of mammals]. / Izmenenie sootnosheniia kvantovo-vezikuliarnykh parametrov pri narushenii sekretsii sinapticheskogo peredatchika v nervno-myshechnom soedinenii mlekopitaiushchego.

To test the vesicular hypothesis of quantum release, some parameters of synaptic vesicles (SV) and miniature end plate potentials (MEPPs) were compared in phrenic neuromuscular junctions of rats poisoned with tetanus toxin (TT). The poisoning with TT that suppresses the transmitter release led to marked changes in the distribution of MEPPs amplitudes and SV diameters as compared to normal, namely to the transformation of unimodal histograms for both parameters to polymodal ones. The transformation was accompanied by a significant increase in variation coefficients of both distributions, thus indicating the disturbances of vesicle-quantum formation. The total number of SV in the poisoned terminal increased by 59% which might reflect both the lifetime situation characteristic for normal and/or real accumulation of the transmitter quanta as a result of the TT-hampered exocytosis through the presynaptic membrane, since during the reactivating action of ouabain, the transmitter release level from the poisoned terminal exceeded that for normal to about the same measure. The results obtained may be regarded as providing evidence in favour of the vesicular hypothesis.

[Statistical analysis of the structure of a train of miniature endplate potentials following different treatments of the process of transmitter secretion]. / Statisticheskii analiz struktury potoka miniatiurnykh potentsialov kontsevoi plastinki pri razlichnykh vozdeistviiakh na protsess sekretsii peredatchika.

The process of transmitter release has been statistically analysed with the use of a rat phrenic nerve-diaphragm preparation in which spontaneous transmitter secretion had been changed by ouabain, 4-aminopyridine and tetanus toxin. In all cases significant deviations of the statistics of miniature end-plate potentials (MEPP) impulse flows from Poisson process and amplitude distributions of MEPP from normal have been obtained. By the statistical characteristics two groups of processes have been distinguished: 1) normal and ouabain where certain consistency of the processes suggests the organization of transmitter release sites and 2) 4-aminopyridine and tetanus toxin where the temporary characteristics of the process in conjunction with the appropriate transformation of MEPP amplitude distribution apparently suggests breakdown of the mechanism of spontaneous synchronization of transmitter quanta release.

[4-Aminopyridine induced spontaneous synchronism of acetylcholine release in the neuro-muscular junction]. / O spontannoi sinkhronizatsii vybrosa atsetilkholina v nervno-myschechnom soedinenii pod vliianiem 4-ami-nopiridina.

The effect of 4-aminopyridine (4-AP) on acetylcholine release was investigated on the rat phrenic diaphragmatic preparations by means of intracellular recording of spontaneous synaptic activity. 4-AP in concentrations of 1.10(-6) to 1910(-3) M did not cause significant shifts in the mean value of frequency and amplitude of miniature end-plate potentials (MEPP). At the same time 4-AP induced appearance of large spontaneous EPP capable of generating distribution of action potentials. 4-AP transformed the character of MEPP amplitude distribution into the polimodal one, the main node being shifted in several cases to the range of lower values. It was concluded that 4-AP can modify the character of acetylcholine release that intensifies the spontaneous synchronism manifestation.