Mechanisms of neutralization of endotoxin by monoclonal antibodies to O and R determinants of lipopolysaccharide.
Explore the source record for details and available documents.
Biomedical subjects
Publications and source records attributed to M Kanoh.
Explore the source record for details and available documents.
We studied the in vitro production of rheumatoid factor (RF) by spleen cells of normal adult mice. IgG RF cross-reactive with rabbit IgG was produced in response to immune complexes of TNP-lipopolysaccharide (LPS) with murine IgG anti-TNP antibody in an Fc-specific manner, but not to a mixture of IgG and LPS. Antibody-uncomplexed LPS induced little IgG RF production, but suppressed the subsequent IgG RF response to antibody-complexed LPS, whereas IgM RF was induced by either LPS or antibody-complexed LPS. The IgG RF production followed as rapid a time course as IgM RF production; the rate of IgG RF production reached its maximum soon after a lag period of 1 day and declined after 5 days. Treatment of splenic B cells from BALB/c mice with anti-Ly-1.2 antibody and rabbit complement resulted in a selective reduction of IgM RF production by 90%, with little effect of IgG RF production. These results suggest that IgG RF is derived primarily from CD5- memory B cells which have been developed in normal mice by an unknown mechanism. Unlike the CD5+ precursor cells for IgM RF, these memory cells are unresponsive to polyclonal stimulation by LPS but are activated by simultaneous stimulation by aggregated Fc epitopes and the mitogenic stimulus from LPS.
Immune complexes of lipopolysaccharide (LPS) with homologous IgG antibody induces rheumatoid factor (RF) predominantly of the IgG class in normal mice, while LPS alone induces mostly IgM RF directed to homologous IgG1. In this study, IgG monoclonal RFs (mRF) were prepared from hybridomas derived from spleen cells of BALB/c mice which were immunized with complexes of TNP-LPS with anti-TNP mouse IgG and their specificity to mouse IgG subclasses was assessed by analysing dissociation kinetics of the ligands due to RF-specific and non-specific interactions. Of the 19 IgG mRFs (11 IgG1, five IgG2a, one IgG2b and two IgG3 types) tested, 14 were directed to either IgG3 or IgG2b or both, while only one exhibited a significant binding capacity to IgG1. Other mRFs, although reactive to rabbit IgG, exhibited little homophilic activity. None of these mRFs reacted strongly with their own isotypes. The results suggest that the IgG RF producing cells are not direct progenies of the IgG1-directed IgM RF-producing cells but may have developed via a rigorous selection process to eliminate clones that produce self-reactive RF.
The authors report a case of an epidermoid in the quadrigeminal cistern in a 40-year-old female who presented with headache and nausea. According to the literature, epidermoids are rarely found in the quadrigeminal cistern. Additional unusual features in this case were the absence of a capsule and T1-weighted magnetic resonance images suggestive of both solid (less intense) and fluid (more intense) components.
A case of recurrent cerebral aneurysm after complete neck clipping is described. A 47-year-old male who presented with headache and nausea underwent neck clipping of a berry aneurysm of the left middle cerebral artery. Ten days later, angiographic findings suggested the presence of a second, large aneurysm adjacent to the first, which suggested misplaced clipping. Reoperation confirmed that a new aneurysm had formed next to the original aneurysm. A possible explanation of the recurrence is as follows. The M1 flowed into the M2 at a right angle. The aneurysmal neck was situated on the distal end of the M1 and the dome protruded antero-inferiorly at an angle of nearly 90 degrees to the long axis of the M1 opposite the origin of the M2. The parent artery bulged slightly, and its wall was thin and reddish, just distal to the aneurysmal neck. Proximal to the neck there was another small bulge, but the wall here was normal. These bulges were coated with Oxycel and Biobond at the time of aneurysmal neck clipping. After clipping, blood flow into the dome was interrupted, and the consequent hemodynamic stress caused the bulges to expand dramatically and form a new aneurysm. The authors conclude that there is a likelihood of early recurrence after neck clipping if the parent artery exhibits such morphological features as observed in this case.
Monoclonal antibodies (2-3E2, 6-3G11, and 7-3H6) against gap junction plaques purified from rat liver were prepared and characterized. Immunoblot analysis of liver gap junctions revealed that all three antibodies reacted with the 27-kDa protein, but not with the 22-kDa one. The 2-3E2 and 6-3G11 antibodies both reacted with the 27-kDa protein in gap junctions purified from livers of the rat, mouse, rabbit, and guinea pig; the 7-3H6 antibody, however, failed to react with the 27-kDa protein from guinea pig liver. The 7-3H6 antibody reacted strongly with the 24- to 26-kDa degradation products of the 27-kDa protein. Indirect immunofluorescence showed that the 6-3G11 and 7-3H6 antibodies both gave the same specific fluorescence labeling on rat liver cryosections, suggesting that these two antibodies recognized the cytoplasmic sites of the 27-kDa protein. Immunoblot analysis of protease-digested fragments from the 27-kDa protein revealed that the 7-3H6 antibody reacted with the 24- and 17-kDa fragments (including portions of the carboxyl-terminal domain of the 27-kDa protein) produced with endoproteinases Arg-C and Lys-C, respectively. Immunoblot analysis of CNBr fragments of the 27-kDa protein revealed that all three antibodies reacted with the 10-kDa fragment, which is thought to be the carboxyl-terminal domain of the 27-kDa protein. These results demonstrate that three monoclonal antibodies recognize different epitopes of the cytoplasmic sites (probably the carboxyl-terminal domain) of the 27-kDa liver gap junction protein.
By studying patients with clinically suspected cerebrovascular occlusive disease using dynamic CT technique, we have shown that contrast peak attenuation of the whole normal cerebral tissue was uniformly reached at the same time within a given individual. On the other hand, the delay of peak time was shown to correlate with some vascular occlusive mechanism. The main implications of delayed contrast peak time can be summarized as follows: Reduced regional blood flow due to stenosis or occlusion of main vessel without tissue damage. Delayed contrast arrival time due to occlusion of main vessel, but with sufficient circulation. Tissue organically injured by cerebrovascular occlusion.
Explore the source record for details and available documents.
Administration of 2,4,6-trinitrophenylated E. coli lipopolysaccharide (TNP-LPS) complexed with mouse IgG antibody to TNP specifically gave rise to a marked production of rheumatoid-like factors (RF) in the recipient mice, in contrast to the low and nonspecific RF production via polyclonal B cell activation by the same dosage of LPS or TNP-LPS alone. The RF activity induced by the LPS immune complexes was associated with both IgG and IgM and directed primarily to the C gamma 2 region as judged by the heterophilic reactivity toward fragments of rabbit IgG. The results suggest that antibody molecules attached to LPS constitute novel epitopic groups on the mitogenic carrier and stimulate B cells in a specific manner to induce the autoantibodies.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
VEPs to number and checkerboard stimuli were measured from F3, F4, P3, P4, Cz, O1 and O2 electrode loci. A trial was composed of 8 successive stimuli: a warning stimulus (WS) and 7 task stimuli. The task stimuli were a hexad composed of 6 identical stimuli (intratrial stimulus positions 1-6) and a single stimulus (position 7). A subject's task was either naming the numbers or pattern matching the checkerboards in the hexad and in position 7. Centrofrontal N140s and parietal N180s to the number and checkerboard stimuli did not change in amplitude across stimulus positions 1-7. Parietal and centrofrontal P350s were large in amplitude at positions 1 and 7 and decreased at positions 2-6. Parietal P270s and centrofrontal P200s to the number and checkerboard stimuli behaved in the same way as the P350s with respect to the stimulus positions. Occipital N180s to the number and checkerboard stimuli were maximum in amplitude at position 1, decreased with stimulus repetition (positions 2-6) and increased at position 7. Occipital P270s to the number and checkerboard stimuli were almost the same in amplitude at position 1. The P270 to the number stimulus increased in amplitude with stimulus repetition (positions 2-6) and decreased at position 7. The P270 to the checkerboard stimulus was the same in amplitude at positions 1-3 increased at positions 4-6 and slightly decreased at position 7. These P270 amplitude changes were interpreted as due to the amplitude changes of the overlapping occipital N250 which reflected task-specific perceptual activities.
Crystalline Taka-amylase A, prepared from Takadiastase, was fractionated into four fractions by DEAE-Sephacel and Concanavalin A-Sepharose column chromatography. The relative weight ratio of the fractions was 90 : 4 : 4 : 2. They had similar molecular weights (51,000), amino acid compositions, and hydrolytic activity against soluble starch, but different phenyl maltosidase activities and electrophoretic mobilities on polyacrylamide gel electrophoresis. Three of the fractions mainly had the high mannose type sugar chain with the sugar composition of Man5-GlcNAc2, but the other fraction had only one N-acetylglucosamine residue as the sugar chain. These results suggested that Taka-amylase A was heterogeneous both in the sugar portions and in the polypeptide portions.
VEPs to six repetitive checkerboard and letter or number stimuli (presented in two triplets) were measured. The task solution process was separated into the store, retention, solve and post-solve stages. Three stimuli in intratrial stimulus positions 1, 2 and 3 were identical and another three in positions 4, 5 and 6 were also identical. The subject's task was either naming the letter-number or matching the checkerboard stimuli in two triplets. For both stimuli, the occipital P270 was almost the same in amplitude as positions 1 and 4. During the memory retention (at position 2) the P270 enhanced for the letter-number stimulus, but not for the checkerboard. During the post-solve stage (at positions 5 and 6) the P270 enhanced for both stimuli. The occipital P270 enhancement seems to correlate with the decrease in the degree of significance of the task relevant stimuli.
In vivo biologic effects of the polymorphonuclear leukocyte-inhibitory factor (PIF) of Bordetella pertussis were tested by using two experimentally induced inflammatory processes in mice. The intravenous injection of a partially purified extract from phase I bacteria strongly inhibited the glycogen-induced peritoneal infiltration of polymorphonuclear leukocytes (PMN) and the Arthus reactions, whereas little inhibitory activity was found in the extract from phase III bacteria. The activity was localized in the outer membrane of phase I bacteria, as was the in vitro PIF activity, and the two activities gave the same behavior in DEAE-cellulose chromatography. Therefore the observed suppression of inflammatory processes in mice is probably due to the inhibitory action of PIF on the function of PMN in vivo.
The outer and inner membranes and cytoplasm of spheroplasts of a strain of phase I B. pertussis were fractionated by density gradient centrifugation. The high density vesicles of the outer membranes isolated had the "Pili" characteristic of the bacteria and the same antigenicty as the bacterial surface. Activities for inhibition of polymorphonuclear leukocytes were also almost exclusively localized in this outer membrane fraction. The histamine-sensitizing activity was more dispersed, but its specific activity was also highest in the outer membrane fraction. These results suggest that molecules carrying these activities, which are probably different entities together with the tissue-adhesive pili, form a virulence complex on the surface of phase I organisms of B. pertussis.
A new factor that inhibited phagocytosis to opsonized targets and chemotaxis of PMN was extracted from B. pertussis cells, and named PMN-inhibitory factor (PIF). Cells in phase I produced 10 times more PIF than those in phase III, and like other phase I-associated components--the hemagglutinin, the histamine-sensitizing factor and agglutinogens--PIF showed degenerative, phenotypic variation during in vitro culture of phase I bacteria. PIF was partially purified by four steps, including adsorption chromatography on Dansyl-aminononamethylene Sepharose. The resulting fraction was heterogeneous but showed little histamine-sensitizing and cytotoxic activities and was free from LPS, the hemagglutinin and a leukocyte agglutinin. The inherent resistance of B. pertussis cells, in either phase I or III, as demonstrated also in the present study, and PIF-mediated defiance against immunological defense mechanism may constitute a complex host-parasite relation in experimental infections with B. pertussis.
Explore the source record for details and available documents.