Mechanisms of the CYNAP phenomenon: evidence in the Bw49/Bw50 model for epitopes with different spatial orientation of antibody

The mechanism of the cytotoxic-negative, absorption-positive (CYNAP) phenomenon was studied using the model of the Bw49/Bw50 split of the BW21 antigen. Anti-Bw49 antibody bound 60% as well to Bw 50 as to Bw49 cells; however, even at a cytotoxic titer of 64 against Bw49 cells, the antibody was not cytotoxic to Bw50 Cells. At equal numbers of antibody molecules bound, the anti-Bw49 antibody activated C4 and C3, and induced lysis for Bw49 but not for the Bw50 cells. These data are consistent with a model in which different spatial orientations for shared epitopes can account for CYNAP reactivity for at least some selected Bw4/Bw6-associated splits of B locus antigens.     

Ascending and descending components of the medial forebrain bundle in the rat as demonstrated by the horseradish peroxidase-blue reaction

Summary The ascending and descending components of the medial forebrain bundle (MFB) were investigated by means of horseradish peroxidase (HRP) with a sensitive substrate. The HRP was injected iontophoretically into the MFB at various levels from the anterior commissure to the posterior hypothalamus. In order to prevent the diffusion of HRP to other brain areas, a double micropipette system was used. The descending components of the MFB are derived from (1) the anterior cingulate area, infra- or prelimbic area, and sulcal cortex, (2) the lateral septal nucleus and diagonal band, (3) the bed nucleus of the stria terminalis, (4) the paraventricular nucleus (5) the substantia innominata, (6) the amygdaloid complex (AM), (7) the ventromedial (VM) and dorsomedial (DM) hypothalamic nuclei, (8) the entopeduncular nucleus and (9) nucleus periventricularis stellatocellularis. The ascending components of the MFB originate in: (1) the medial preoptic nucleus, (2) the nucleus periventricularis stellatocellularis and rotundocellularis, (3) the posterior hypothalamic nucleus, (4) the parafascicular nucleus, (5) the ventral premammillary nucleus, (6) the substantia grisea periventricularis, (7) the lateral habenular nucleus, (8) the VM and DM, (9) the paratenial nucleus, (10) the AM and (11) the arcuate nucleus.Abbreviations used in Figures and Tables a nucleus accumbens - abl nucleus amygdaloideus basalis, pars lateralis - abm nucleus amygdaloideus basalis, pars medialis - ac nucleus amygdaloideus centralis - AC anterior cingulate area - al nucleus amygdaloideus lateralis - am nucleus amygdaloideus medialis - ar nucleus arcuatus - CC tractus corporis callosi - CSDV commissura supraoptica dorsalis, pars ventralis - DB diagonal band - DM nucleus dorsomedialis hypothalami - EP nucleus entopeduncularis - ha nucleus anterior hypothalami - hl nucleus lateralis hypothalami - hp nucleus posterior hypothalami - IL infralimbic area of frontal cortex - lh nucleus habenulae lateralis - LH₁ medial forebrain bundle (MFB) at the level of commissura anterior - LH₂ lateral preoptic area - LH₃ MFB at the level of the nucleus anterior hypothalami - LH₄ MFB at the level of the nucleus ventromedialis hypothalami - LH₅ MFB at the level of the nucleus posterior hypothalami - MFB medial forebrain bundle - pf nucleus parafascicularis - PL prelimbic area of frontal cortex - pol nucleus preopticus lateralis - pom nucleus preopticus medialis - posc nucleus preopticus, pars suprachiasmatica - pt nucleus parataenialis - pv nucleus premamillaris ventralis - PV nucleus paraventricularis - pvs nucleus periventricularis stellatocellularis - pvr nucleus periventricularis rotundocellularis - SC sulcal cortex - SGPV substantia grisea periventricularis - SI substantia innominata - SL lateral septal nucleus - ST bed nucleus of stria terminalis - sum nucleus supramamillaris - TO tractus opticus - tmm nucleus medialis thalami, pars medialis - VM nucleus ventromedialis hypothalami The nomenclature used in this paper is according to König and Klippel's Stereotaxic Atlas (1967).     

Bovine colostrum supplementation does not affect plasma buffer capacity or haemoglobin content in elite female rowers

It has been reported that bovine colostrum (BC) supplementation improves buffer capacity () during exercise, but whether the improvement results from changes in tissue and/or blood buffer systems has not been determined. The purpose of the present study was to examine the effect of supplementation with BC on blood buffer systems. Thirteen elite females rowers were supplemented with 60 g·day^–1 of either BC (n=6) or whey protein (WP, n=7) during 9 weeks of pre-competition training in a randomised, double-blind, placebo-controlled, parallel design. All subjects undertook the study as a group and completed the same training program. Resting haemoglobin (Hb) concentration and plasma buffer capacity (p) (determined by titration with HCl) were measured pre- and post-supplementation. There were no differences in macronutrient intakes (P>0.56) or training volumes (P>0.99) between BC and WP during the study period. There were no differences in Hb [BC 13.28 (0.28) mg·dl^–1, WP 13.70 (0.26) mg·dl^–1; P=0.45] or p [BC 14.8 (1.1) nmol HCl·ml^–1·pH^–1, WP 14.8 (0.5) nmol HCl·ml^–1·pH^–1; P=0.68] between groups at week 0. p increased in both groups during the study period (P<0.001), but the increases were not significantly different between groups (P=0.52). Hb did not change significantly in either group (P=0.35). These data indicate that supplementation with BC does not affect p or Hb. We therefore suggest that adaptations in tissue buffer systems are responsible for the previously reported increases in buffer capacity that result from BC supplementation.     

Computer Imaging Analysis of Glomerular Extracellular Components in Patients with IgA Nephropathy

Computer imaging analysis was used for quantitative evaluation of the extents, amounts and distributions of glomerular extracellular components, such as the 7S and NC 1 domains of type IV collagen, laminin (LN), fibronectin (FN) and IgA, in glomeruli from patients with IgA nephropathy. Renal biopsy specimens from 13 patients with IgA nephropathy were incubated with mouse monoclonal antibodies against the FN or non collagenous (NC 1) domain of type IV collagen or polyclonal antiserum against the LN or 7S domain of human type IV collagen, and then stained with appropriate dilutions of FITC labeled anti mouse Ig antisera. Marked staining of the 7S or NC 1 domain of type IV collagen, LN or FN was detected in the glomerular capillary walls and/or mesangial areas in patients with IgA nephropathy. In particular, a prominent increase of FN was observed in the subendothelial regions of glomerular capillary walls, i.e. mesangial interposition, in the moderate or advanced stage of IgA nephropathy. Therefore, computer imaging analysis was shown to be useful for the quantitative determination of such components distributed in glomeruli from patients with IgA nephropathy. Acta Pathol Jpn 39: 296 305, 1989.     

老年人脑白质疏松症血液流变性及血液成分的改变

对３８例老年脑白质疏松症（ＬＡ）患者进行了部分血液流变性和血液成分指标的测定。结果：与健康者比较，ＬＡ患者全血粘度、血浆粘度、ＲＢＣ刚性指数和聚集指数、纤维蛋白原显著增高，ＲＢＣ变形能力明显降低，血Ｈｂ、ＭＣＶ、ＭＣＨ、ＭＣＨＣ、ＲＤＷ－ＣＶ显著增高。提示：血液流变性异常和红细胞老化参与了ＬＡ的发生。设法纠正患者高粘和高凝状态、提高红细胞变形能力有益于阻止该病的进展     

Auditory event-related potentials during stage 2 NREM sleep in humans

SUMMARY  Event-related potential (ERP) recordings were used to investigate the nature of auditory stimulus evaluation during stage 2 sleep. Frequent and rare stimuli, differing in intensity and frequency, were presented to six adult subjects while awake and asleep. The latency and voltage distribution of one of the long-latency components evoked during sleep resembled the P3 component evoked while awake. However, it was attenuated in voltage and superimposed on N3, a large late negative component, most probably the slow potential of the K complex. The identification of a P3-like potential during sleep suggests that the P3 potential is not solely a marker of active cognitive processes, but contains a small component which reflects automatic, pre-attentive evaluation of deviant stimuli.     

A Morphological and Immunohistochemical Study of Lymphoid Germinal Centers in Synovial and Lymph Node Tissues from Rheumatoid Arthritis Patients with Special Reference to Complement Components and Their Receptors

Rheumatoid arthritis (RA) is one of the immune complex (IC) diseases in which lymphoid germinal centers (GCs) are found in the synovial tissue. Simultaneously, patients with RA often show swelling of lymph nodes. The morphology and function of the lymph node GCs in patients with RA is not clear. The aim of this study was to evaluate the differences in morphology and immunoreactions to complement (C) components, their receptors, and lgM-rheumatoid factor (RF) between synovial GCs and lymph-node GCs in RA. Furthermore, the relationship between these immuno-reactive substances and follicular dendritic cells (FDCs) in GCs was investigated. The tissues examined were 41 RA synovial specimens, seven RA lymph nodes with massive lymphadenopathy, and 10 non-RA lymph nodes. The number of synovial GCs was relatively decreased in comparison with lymph-node GCs in RA, and the diameter of each synovial GC was smaller than that of each lymph-node GC. The synovial GCs were edematous and less cellular, and moreover, those from RF-seronegative cases were smaller than those from RF seropositive cases. On the other hand, the lymph-node GCs in RA were larger, more cellular and hyperplastic, but contained more tingible-body macro-phages (TBMs) and neutrophils. In the GCs of both synovial tissues and lymph nodes in RA, early C components (C1q, C4, C3c, C3d), IgM RF, and C3b receptor (C3bR) and C3d receptor (C3dR) were expressed as a lacy network by light microscopy, and were demonstrated on the surfaces of FDCs and lymphocytes, and in the intercellular spaces by electron microscopy. Furthermore, immuno-staining for dendritic reticulum cells (DRC, DAKO DRC1) was observed in a lacy pattern by light microscopy and on the cell surface of FDCs by electron microscopy. In the GCs of non-RA lymph nodes, early C components, C3bR, C3dR, and DRC showed a similar reaction pattern, but IgMRF did not. Consequently, no marked difference in immunoreactions in the GCs, except for the immunoreactions of late C components, was found between synovial tissues and lymph nodes in RA. On the basis of these findings, we discuss the possibility of the presence of a RF-IC.     

Frequency domain models of the EEG

The structure of the normal resting EEG crosspectrum SVV(omega) is analyzed using complex multivariate statistics. Exploratory data analysis with Principal Component Analysis (PCA) is followed by hypothesis testing and computer simulations related to possible neural generators. The SVV(omega) of 211 normal individuals (ages 5 to 97) may be decomposed into two types of processes: the xi process with spatial isotropicity reflecting diffuse, correlated cortical generators with radial symmetry, and processes that seem to be generated by more spatially concentrated, correlated sources. The latter are reflected as spectral peaks such as the process. The eigenvectors of the xi process are the Spherical Harmonic Functions which explains the recurring pattern of maps characteristic of the spatial PCA of qEEG data. A new method for estimating sources in the frequency domain which fits dipoles to the whole crosspectrum is applied to explain the characteristics of the localized sources.     

Human cerebral potentials evoked by CO2 laser stimuli causing pain

Summary Brief radiant heat pulses, generated by a CO₂ laser, were used to activate slowly conducting afferents in the hairy skin in man. In order to isolate C-fibre responses a preferential A-fibre block was applied by pressure to the radial nerve at the wrist. Stimulus estimation and evoked cerebral potentials (EP), as well as reaction times, motor and sudomotor activity were recorded in response to each stimulus. With intact nerve, the single supra-threshold stimulus induced a double pain sensation: A first sharp and stinging component (mean reaction time 480 ms) was followed by a second burning component lasting for seconds (mean reaction time 1350 ms). Under A-fibre block only one sensation remained with characteristics and latencies of second pain. The heat pulse evoked potential consisted of a late vertex negativity at 240 ms (N240) followed by a prominent late positive peak at 370 ms (P370). Later activity was not reliably present. Under A-fibre block this late EP was replaced by an ultralate EP beyond 1000 ms, which in the conventional average looked like a slow halfwave of 800 ms duration. This potential was distinct from eye movements, skin potentials or muscle artefacts. With cross-correlation methods waveforms similar to the N240/P370 were detected in the latency range from 900 to 1500 ms during A-fibre block, indicating a much greater latency jitter of the ultralate EP. Latency corrected averaging with a modified Woody filter yielded a grand mean ultralate EP (N1050/P1250), the shape of which was surprisingly similar to the late EP (N240/P370). The similarity of these components indicates that both EPs may be secondary responses to afferent input into neural centers, onto which myelinated and unmyelinated fibres converge. Such convergence may also explain through the known mechanisms of short term habituation and selective attention, why ultralate EPs are not reliably present without peripheral nerve block.     

Unrestricted principal components analysis of brain electrical activity: Issues of data dimensionality,artifact, and utility

Summary Principal components analysis (PCA) was performed on the 1536 spectral and 2944 evoked potential (EP) variables generated by neurophysiologic paradigms including flash VER, click AER, and eyes open and closed spectral EEG from 202 healthy subjects aged 30 to 80. In each case data dimensionality of 1500 to 3000 was substantially reduced using PCA by magnitudes of 20 to over 200. Just 20 PCA factors accounted for 70% to 85% of the variance. Visual inspection of the topographic distribution of factor loading scores revealed complex loadings across multiple data dimensions (time-space and frequency-space). Forty-two non-artifactual factors were successful in classifying age, gender, and a separate group of 60 demented patients by linear discriminant analysis. Discrimination of age and gender primarily involved EP derived factors, whereas dementia primarily involved EEG derived factors. Thirty-eight artifactual factors were identified which, alone, could not discriminate age but were relatively successful in discriminating gender and dementia. The need to parsimoniously develop real neurophysiologic measures and to objectively exclude artifact are discussed. Unrestricted PCA is suggested as a step in this direction.Acknowledgements: This work was supported in part by NIA program project PO1AG049853 to M. Albert and the Mental Retardation Program Project P30HD18655 to J.J. Volpe. We thank our qEEG technologists Adele Mirabella, Susan Katz, Ellen Belles, and Marianne McGaffigan as well as our research secretaries for their unflagging support.