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Biomedical subjects

G D Jackson

Publications and source records attributed to G D Jackson.

At least 91 records · Page 5Linked to original sources

Functional mapping of activated human primary cortex with a clinical MR imaging system.

Functional activation of the human brain can be visualized with magnetic resonance (MR) imaging, but most studies so far have used echo-planar imaging or magnetic fields of 2 T and above, neither of which are at present widely available. The authors used a standard 1.5-T MR imaging system to map regions of the brain that are activated with visual and motor tasks, using a long echo time (60 msec) fast low-angle shot sequence. Eleven visual and 14 motor studies were performed, and activation was seen in all cases. Up to 15% signal intensity change was apparent in gray matter but not in white matter. The precise anatomic location and extent of activation were defined by reference to T1-weighted images acquired during the same examination. This method of relating brain structure to function uses equipment that is widely available, which has considerable implications for the investigation of many neurologic and neurosurgical diseases and for our understanding of brain function and dysfunction.

Adult↗

Detection of hippocampal pathology in intractable partial epilepsy: increased sensitivity with quantitative magnetic resonance T2 relaxometry.

Abnormal T2-weighted signal intensity in the hippocampus may be difficult to detect visually, and T2 mapping provides an objective means of assessing signal abnormality. We investigated 50 adult outpatients suffering from intractable partial epilepsy with MRI optimized to detect hippocampal and cortical gray matter abnormalities, and with MR T2 relaxation mapping. The range of normal hippocampal T2 relaxation times is small (99 to 106 msec), and the measurements are reproducible between observers. There were abnormal hippocampal T2 relaxation times in the hippocampus ipsilateral to the site of seizure origin in 70% of patients studied, with the more severe abnormality in the ipsilateral hippocampus in all cases. All hippocampal T2 measurements greater than 116 msec were associated with temporal lobe epilepsy and pathologic or MRI evidence of hippocampal sclerosis, or both. Bilateral abnormalities were present in 29% of cases with hippocampal sclerosis.

Adolescent↗

Rat secretory component binds poorly to rodent IgM.

Our previous studies and those of others indicated that human secretory component (SC), the five domain extracellular portion of the poly Ig receptor, binds avidly to both pIgA and IgM. In this study we report that in rodents, SC binds primarily to pIgA. Rat secretory component was isolated from bile and radiolabeled to known specific activity with 125I. Radiolabeled rat SC was incubated with rat and mouse monoclonal proteins for 1 h at room temperature and overnight at 4 degrees D. Binding of 125I-rat SC to Ig was determined in two ways: 1) immunoprecipitation of putative 125I-rat SC-Ig complexes with anti-L chain antibodies; 2) HPLC gel filtration on an analytical TSK 4000 column that separated free 125I-rat SC from 125I-rat SC bound to Ig. Both methods of analysis yielded similar results. Rat and mouse polymeric (p) IgA bound rat SC with high avidity, although the binding activity of the IgM from either species was virtually nil. The number of SC-binding sites on rat polymeric Ig was determined by immunoprecipitation of mixtures of rat pIg with saturating concentrations of 125I-rat SC and yielded values of 1.0 and 0.05 for rat pIgA and IgM, respectively. The significance of these findings with respect to the biologic function of the pIg R in rodents and the nature of the pIg R-binding site on pIg is discussed.

Animals↗

Further evidence that hepatic sources confer biliary antibody in the rat.

The notion that bile-dedicated antibody is made within the liver by migratory antibody-forming cells (AFC) was examined further in rats. Livers from immunized animals were removed to perfusion in isolation so that plasma influences on bile antibody would be obviated. Antibody was secreted for at least 5 hr by the livers of rats that had received intravenous (i.v.) or intra-Peyer's patch (IPP) immunization with horse erythrocytes. After initially declining, the titres stabilized at 5-8% of the starting value for IPP-immunized rats and at 0.8% for i.v.-immunized animals, levels that were then sustained. In other experiments, the biliary antibody output was measured in immunized rats in the period immediately following splenectomy, an expedient that would deny the liver any newly formed AFC. Splenectomy during spleen-based, IgM antibody responses led to bile titres falling, over about 12 hr, to 21% of initial values. This level was then maintained for at least another 12 hr. Serum titres over this period remained static. Lastly, the bile ducts of immunized rats were ligated to test whether locally made antibody that was destined for bile could be forced instead to reflux to blood. Biliary obstruction during IgM responses to horse erythrocytes and pneumococcal polysaccharide, type 3, was found to raise significantly serum antibody titres. For pneumococcal polysaccharide, the serum response was also noticeably prolonged. These findings are consistent with the biliary antibody of immunized rats being constituted, in part, from local sources and not from plasma alone.

Animals↗

Movement of IgM antibody from blood to bile in rats.

The movement from blood to bile of passively injected autologous IgM antibody against horse erythrocytes was studied in rats. Both native and neuraminidase-treated antibody entered bile intact, with the peak titers for both measured between 60 and 90 min after injection. A small part (0.38%) of the injected dose of native antibody and 1.05% of the asialo-IgM antibody appeared in bile over 24 hr. These recoveries represented only a small fraction of the activity, which apparently disappeared from serum over the period. The pathways used by IgM antibody to enter bile were partially assessed. Prior injection of fetuin was found to abrogate the biliary secretion of native antibody and to significantly reduce the recovery of asialo-antibody in bile. In contrast, the presence of asialofetuin reduced (but not significantly) the secretion of native antibody and markedly changed the kinetics of appearance of asialo-IgM activity in bile. Some candidate routes to bile can be excluded as unlikely. The parahepatocellular pathway to bile canaliculi appears uninvolved because the secretion of antibody is slow and the inhibitory effects of fetuin argue against secretory component-mediated transport. Instead, two secretory pathways appear to be present. The first appears to be available to both native and asialo-IgM antibody, and may involve the peribiliary capillary plexus. The second route to bile is available to asialo-IgM antibody alone and is probably initiated by binding to the hepatic asialoglycoprotein receptor.

Animals↗

The occurrence and sources of natural antibody in human bile and serum against the O antigens of two Escherichia coli serotypes.

Paired serum and bile samples from normal subjects as well as patients with biliary disease were tested for natural antibody to two individual Escherichia coli O antigens by ELISA. Serum antibody was most commonly of IgM and IgG class. Antibody was less frequently detected in bile and was more commonly IgM than IgA, with IgG activity detected infrequently. Little relation was apparent between antibody in paired samples; activity could be present in both serum and bile or in either fluid alone. Titres in paired samples also did not correspond when 'normalized' with respect to the concentrations of relevant isotypes; bile was frequently enriched for natural antibody as a proportion of total immunoglobulin compared with serum. Secretory component-bound antibody was detectable in some biles that contained IgA and/or IgM activity and in the serum of 33% of subjects with biliary disorders but not in normal sera. A series of paired samples taken from three individuals was also examined for antibody against each subject's own intestinal commensal E. coli. Serum IgM and IgG activity was present in all samples, but antibody in bile was less frequent and was of IgM or IgA class. These results suggest that natural antibody in human bile occurs independently of antibody in serum and that it is substantially derived from local sources.

Adolescent↗

Hippocampal sclerosis can be reliably detected by magnetic resonance imaging.

Two independent blinded observers reported the preoperative MRIs in a series of 81 consecutive patients with intractable temporal lobe epilepsy who were undergoing temporal lobectomy. We then compared the nature and lateralization of the MRI abnormalities with the pathologic diagnosis and the side of lobectomy. The MRI criteria of hippocampal sclerosis were an increased T2-weighted signal and the signal's confinement to a unilaterally small hippocampus. Imaging was performed in coronal and axial planes, specially orientated along and perpendicular to the long axis of the hippocampal body. We found diagnostic MRI abnormalities in 25 of the 27 cases with pathologically proven hippocampal sclerosis (sensitivity 93%, specificity 86%). In addition, we detected all 13 foreign tissue lesions on MRI. Overall, we detected lateralized lesions on MRI that correctly predicted the side of the epileptogenic temporal lobe in 72 cases (89%), with 2 possible errors. A learning effect in appreciating the relatively subtle MRI changes of hippocampal sclerosis was apparent in our later cases, as shown by an improved correlation between the 2 observers. This study demonstrates that hippocampal sclerosis can be identified on MRI with a high degree of sensitivity and specificity.

Brain Neoplasms↗

Antibody responses in the liver and bile of rats injected with horse erythrocytes.

The intravenous injection of 1 ml of a 0.1% (or higher %) suspension of horse red blood cells (HRBC) into rats results in the appearance of high levels of agglutinating activity in bile as well as serum. Lower doses of HRBC induce reduced responses in both fluids, demonstrating that the biliary response is as dose-dependent as the serum response. The presence of IgM anti-HRBC antibody forming cells (AFC) in the liver in numbers equivalent to those detected in the spleen at day 6 of the study suggests them to be the most likely source of the biliary antibody. Also, the injection of HRBC into other parenteral sites (intramuscular [i.m.], intraperitoneal [i.p.] and intrathoracic cavity [i.t.]) results in a biliary response which is considered to originate from the IgM-, IgG- and IgA-anti-HRBC AFC detected in the liver, again in numbers approximating those detected in the spleen. Splenectomy of rats immunized i.p., i.m. and i.t. had only a minimal effect on the liver and biliary responses, indicating that AFC arising in peripheral lymphoid tissues can also relocate in liver. It is concluded that the liver is a major site of antibody synthesis following parenteral immunization leading to substantial levels of antibody being secreted into the gastrointestinal tract.

Animals↗

Appearance of IgG and IgA antibodies in human bile after tetanus toxoid immunization.

Humans immunized intramuscularly with one dose of tetanus toxoid exhibited IgG, and in some cases IgA antibody, in their bile as well as serum. Both isotypes appeared in bile transiently with titres declining after about day 10 for both classes. These kinetics resembled those of the serum IgA response but were markedly different to those for IgG antibody in serum. Measured IgG titres in bile were between 0.07 and 4.2% of those in paired sera, and IgA titres were between 6.8 and 124% of sera. Peak responses in bile, while generally of smaller size, exceeded those of paired sera when expressed as antibody/mg of IgG or IgA present. This calculation showed that during the peak response bile was up to nineteen-fold more abundant in IgG antibody than was serum taken at the same time, and up to forty-five-fold more for IgA. Enrichment of antibody in bile is not consistent with the Ig of bile being solely conferred by plasma, and may mean the involvement of local synthesis too. This study indicates that tetanus toxoid immunization of humans results in biliary antibody and raises the possibility of intra-hepatic antibody production for export to the intestinal tract in man.

Adolescent↗

Simultaneous occurrence of anomalous cardiac and tracheal bronchi: a case study.

A rare case of a combination of an accessory cardiac bronchus and a right tracheal bronchus found incidentally is presented, together with a discussion of the anatomy, embryology, and possible clinical ramifications of these anomalies. The incidence of these anomalies occurring in 2,000 tomographic studies of the chest at University of South Alabama Medical Center is cited.

Bronchi↗

Antigens involved in resistance to mucosal association by Vibrio cholerae.

Resistance to growth of Vibrio cholerae at the mucosa of blind intestinal loops developed in rats after intestinal or parenteral exposure to live organisms or other antigenic materials. Simultaneous serological studies suggested that neither serum vibriocidal activity nor intestinal mucus antibodies are likely to provide a direct test of antibacterial immune status. Challenge of rats 4 weeks after one dose of antigen may reveal a form of immunity that is not related to antibodies in the intestine and possibly is analogous to long-term immunity expressed in man following infection with the organism. This immunity has not been attributed to lipopolysaccharide (LPS) antigen and does not appear to involve flagella-associated antigens; involvement of antigens other than LPS, such as protein antigens of the outer membranes of V. cholerae, has not yet been substantiated. Separation of monomeric sub-units of outer-membrane proteins by hydrophobic interaction high pressure liquid chromatography has revealed significant quantitative differences among preparations derived from the common serotypes of the organism. These differences may be sufficient to explain the better protection observed when homologous serotypes were used for immunisation and challenge in the long-term resistance model.

Animals↗

Antibody synthesis in the rat liver: an association between antibody-forming cells in the liver and biliary antibodies following intravenous injection of horse erythrocytes.

The transient appearance of IgM in the bile of rats injected intravenously with horse erythrocytes (HRBC) correlated with the occurrence of anti-HRBC IgM-secreting cells in the liver. Both responses were reduced in animals splenectomised at the time of immunisation. When rats were given 2 injections of HRBC spaced by 28 days, IgG, IgA and IgM antibody-forming cells (AFC) were detected in the liver along with IgM and non-IgM anti-HRBC antibody in bile. There was a 10-fold increase in the total numbers of mononuclear cells (MNC) retrievable from the liver at the height of the biliary antibody response, the majority of which were not AFC. These results suggest that antigen entering the spleen stimulates the release of a population of MNC which may localise in the liver and that a minor portion of these produces specific antibody which is secreted into bile.

Animals↗

Antibody synthesis in the rat liver: a source of biliary IgM, IgA and IgG following injection of horse erythrocytes into the intestine or Peyer's patches.

Intestinal injection of HRBC into rats leads to: 1. an anti-HRBC response in serum and bile - HA activity in bile is associated with IgM, IgG and IgA. 2. an increase in total IgM in bile. 3. the presence of IgM, IgA and IgG AFC in liver. Equivalent AFC responses occur in livers of splenectomized rats. It is concluded that the results are consistent with the proposal that the liver is a site for localization of antibody-secreting cells which enter the blood and that these cells are a source of biliary antibody.

Animals↗

A role for the spleen in the appearance of IgM in the bile of rats injected intravenously with horse erythrocytes.

The i.v. injection of the particulate antigens horse red blood cells (HRBC) and Salmonella enteritidis into rats results in the appearance of high levels of IgM agglutinating antibody in the serum and bile. This is in contrast to the appearance of specific IgA antibodies in bile after the injection of antigen into the Peyer's patches. At the height of the response, a fivefold to 10-fold increase in total IgM was found in bile, whereas there was no increase in IgA or in total protein levels. The biliary IgM was not associated with secretory component. Studies aimed at revealing the source of the IgM showed that neither immunized nor nonimmunized rats were able to transport 131I-rat IgM, but both groups were equally efficient at transporting 125I-rat IgA. Furthermore, specific anti-HRBC antibody could not be detected in the bile of rats that were injected with a high titer serum, indicating that blood is unlikely to be the source. Splenectomy of rats at the time of the injection of antigen, at 3 days after immunization had abrogated the biliary response, and at 5 days resulted in rapid decline in existing specific antibody level. Involvement of the spleen was additionally implicated when it was shown that injection of animals with immune spleen cells gave rise to specific antibodies in serum and bile. On the basis of these experiments, it is proposed that antigen entering the blood stream can stimulate a population of cells in the spleen that emigrates to the liver, where the cells localize and secrete IgM into bile.

Animals↗

Intestinal antibodies in rats following exposure to live Vibrio cholerae.

Indirect enzyme-linked immunosorbent assay methods were used to characterize the primary, secondary and tertiary antibody responses of rats to the lipopolysaccharide (LPS) and heat-sensitive surface-associated (HSSA) antigens of V. cholerae in the major immunoglobulin classes of serum, intestinal mucus and bile following intestinal injections of live organisms. Antibody production following the first injection was limited to the IgG and IgM classes of serum and the IgA class of bile but a second dose given 14 days later induced significant responses in all Ig classes of the three materials. Two contacts with the organism established effective, possibly long term, memory; large increases in serum IgG and intestinal mucus IgG and IgA anti-LPS antibody concentrations occurred when the organism was given 6 weeks later, but anti-HSSA production following the third injection was not significantly greater than during the secondary response. The results also suggest that while anti-LPS antibodies of all three Ig classes are formed in the intestinal lymphoid tissues, local anti-HSSA antibody is restricted to the IgA and IgG classes. Excretion of antibodies in bile does not directly correlate with responses in local and peripheral lymphoid tissues. It is suggested that the hepato-biliary system may be as important to antibody-mediated immunity in the intestine as are the active and passive transepithelial mechanisms of antibody secretion.

Animals↗