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Biomedical subjects

E Kim

Publications and source records attributed to E Kim.

At least 289 records · Page 16Linked to original sources

[The effect of individual MHC subregions (RT1.A,B,D) and treatment with anti-RT1.D monoclonal antibody on survival of pancreatic islet allograft in the rat].

The present studies were undertaken to investigate the effect of the individual MHC subregions (RT1.A,B,D) and pretreatment with anti-RT1.D monoclonal antibody (MoAb) on survival of pancreatic islet allograft, using inbred, congenic, and recombinant rats which have different classes of histocompatibility barriers. Pancreatic islets were transplanted soon after isolation and after the treatment with anti-RT1.D MoAb. All syngenic islet allograft survived more than 90 days. The mean survival time (MST) of RT1.B,D incompatible combination (7.6 +/- 2.5 days) was significantly shorter than that of RT1.A incompatible combination (greater than 39.6 +/- 18.7 days). The MST of RT1.D incompatible combination (7.4 +/- 3.0 days) was significantly shorter than that of RT1.B incompatible combination (24.4 +/- 5.6 days). The MST of islet allograft, treated with donor specific and cytotoxic anti-RT1.D MoAb, in full-RT1 incompatible combination was prolonged up to 42.6 days (+/- 17.3 SD); this was statistically significant, when compared with that of untreated islet allograft in same combination (8.4 +/- 2.5 days). These results indicated that RT1.D region differences had a much more important role than RT1.A or RT1.B subregion differences in order to induce a strong rejection reaction in rat pancreatic islet allograft, and the treatment of islet with anti-RT1.D MoAb was very useful to prevent an acute rejection.

Animals↗

Lipid peroxidation and phospholipase A2 activity in liposomes composed of unsaturated phospholipids: a structural basis for enzyme activation.

The effect of lipid peroxidation on membrane structure and phospholipase A2 activity was studied using liposomes composed of bovine liver phosphatidylcholine (PC) and phosphatidylethanolamine (PE). The phospholipids were mixed at set ratios and sonicated to yield small unilamellar vesicles. The liposome preparations were subjected to lipid peroxidation as induced by cumene hydroperoxide and hematin. Under these conditions, a sharp increase in lipid peroxidation was noted over a 30 min incubation period and was accompanied by loss of polyunsaturated fatty acids (PUFA). Liposomes enriched in PE were most extensively peroxidized with a preferred oxidation of this phospholipid. The extent of PC oxidation was also greater in liposomes containing the largest proportions of PE. Analysis of liposome anisotropy, via steady-state fluorescence polarization of diphenylhexatriene indicated that progressive increases in either PE content or the level of lipid peroxidation increased the apparent microviscosity of the vesicles. Moreover, lipid peroxidation increased anisotropy more effectively than variations in the ratios of PE vs. PC. Thus, peroxidation of 5-10% of the phospholipids produced the same anisotropy increase as a 20% increase in the ratio of PE vs. PC. Analysis of vesicle turbidity suggested that fusion was also more readily achieved through lipid peroxidation. When liposomes were incubated with 0.4 U/ml of snake venom phospholipase A2, a direct correlation was found between the degree of lipid peroxidation and the extent of phospholipid hydrolysis. The more unsaturated phospholipid, PE, was most extensively hydrolyzed following peroxidation. Increasing the proportion of PE also resulted in more extensive phospholipid hydrolysis. These findings indicate that lipid peroxidation produces a general increase in membrane viscosity which is associated with vesicle instability and enhanced phospholipase A2 attack. A structural basis for membrane phospholipase A2 activation as a consequence of lipid peroxidation is discussed in light of these findings.

Animals↗

Hepatic amyloidosis--two cases report.

Amyloidosis is classified according to the distribution pattern of amyloid deposition sites and associated diseases. Hepatic amyloidosis is not infrequent, although rarely causes clinical liver disease. We report two cases of amyloidosis diagnosed by liver biopsy. One presented with symptoms related almost to the liver disease, such as jaundice, hepatomegaly and indigestion. Echocardiogram revealed hypertrophic cardiomyopathy, suggesting cardiac involvement of the amyloidosis. The patient died of hepatic failure. The other case was found in a patient with an end stage renal disease. Features of congestive heart failure in this case may reflect cardiac involvement. The pattern of hepatic amyloid deposition in both of these cases was diffuse perisinusoidal. The predominant intralobular deposition suggests that these are amyloidosis of the secondary type.

Amyloidosis↗

Degradative intracellular transport of antisecretory component in cultured hepatocytes. An alternate pathway for the immunoglobulin A receptor.

The liver efficiently transports dimeric immunoglobulin A (dIgA) from blood to bile in a direct, nonlysosomal pathway involving smooth-surfaced vesicles. Secretory component (SC), the plasma membrane receptor for dIgA, is released into bile still bound to its ligand by disulfide bridges. Rabbit IgG antirat SC binds specifically to plasma membrane SC, yet the biliary secretion of anti-SC is markedly lower than that of dIgA, suggesting that the IgG antibodies utilize an alternate transhepatocellular pathway. Uptake of commercially available antihuman SC conjugated to horseradish peroxidase was examined by quantitative electron microscopic immunocytochemistry using primary rat hepatocyte monolayer cultures. Coincubation with human polymeric IgA, rabbit antiserum to rat SC, free human SC, human secretory IgA, and rat bile, all significantly suppressed uptake of anti-SC-horseradish peroxidase, thus demonstrating the specificity of the labeled antibody. Coated vesicles accounted for greater than 70% of the total uptake of either the anti-SC-horseradish peroxidase preparation or colloidal gold-labeled IgG antirat SC. Both compounds could also be observed in other structures associated with the degradative pathway, i.e., multivesicular bodies and lysosomes. Moreover, the extent to which 125I-anti-SC was degraded was significantly greater than that of 125I-dIgA. These data demonstrate that dIgA and anti-SC utilize different intracellular pathways, with anti-SC undergoing lysosomal degradation.

Animals↗

Phospholipase A2 dependent release of fatty acids from peroxidized membranes.

Unilamellar vesicles (liposomes) consisting of liver phosphatidylcholine and phosphatidylethanolamine were used as model membranes and subjected to lipid peroxidation. Following peroxidation samples were treated with phospholipase A2 from snake venom and subsequently analyzed for products of lipid peroxidation and of phospholipase A2 action. A significantly increased susceptibility to phospholipase A2 was noted for liposomes subjected to peroxidation, as compared to controls, which correlated with the extent of lipid peroxidation measured by the formation of thiobarbituric acid reacting products and conjugated dienes. Low levels of peroxides were detected in control liposomes and these peroxidases were rapidly cleaved by phospholipase A2, such that nearly 40% of the total peroxide content was associated with free fatty acids after l5 min incubation. Oxidized liposomes contained over seven fold the level of lipid peroxidation products, and the were also rapidly cleaved by phospholipase A2 where over 50% were recovered as free fatty acids following l5 min of exposure to phospholipase A2. Along with this high order of removal of oxidized fatty acids, a marked hydrolysis of intact fatty acids was also observed. The extent of fatty acid release was roughly correlated with the degree of fatty acid unsaturation. A substantial increase in the release of arachidonic acid was found when peroxidized membranes were analyzed.

Fatty Acids↗

Objective evaluation of local xenogeneic graft-versus-host reaction by computerized radioisotope imaging (CRI).

The local xenogeneic graft-versus-host reaction (GVHR) assay has been used clinically to evaluate cellular immune competence and experimentally to monitor the immunomodulatory effects of several drugs. By employing a computerized radioisotope imaging (CRI) technique, we were able to perform the assay with smaller numbers of mononuclear cells (MNC) and to rid it entirely of any bias. Measuring the local GVHR by CRI compares well with the conventional measurement of the volume (correlation coefficient r = 0.619; P less than 0.001). A clear-cut distinction was documented between normal donors and cancer patients (P less than 0.001) when 10 X 10(6) or more MNC were used in the assay. This is an improvement over the previous, conventional testing of local GVHR which required injection of 20 X 10(6) MNC in order to achieve a similar resolution. The indications for the presence of immune competence have therefore been redefined using the local GVHR index as determined by CRI according to the scale of MNC injected. Thus, immunocompetence is considered present if the CRI index is greater than or equal to 1.2 for 10 X 10(6) MNC, greater than or equal to 2.0 for 15 X 10(6) MNC and greater than or equal to 2.6 for 20 X 10(6) MNC.

Animals↗

Radioimmunodetection of primary and metastatic ovarian cancer using radiolabeled antibodies to carcinoembryonic antigen.

131I-labeled goat immunoglobulin G (IgG) prepared against carcinoembryonic antigen (CEA) was administered at an average dose of 1.0 mCi (180 to 250 microgram IgG protein) to patients with ovarian tumors in order to evaluate this method of tumor detection and localization, termed the radioimmunodetection of cancer. All primary cancers in 13 patients could be localized, whereas the metastases in six of nine cases could be imaged by external scintigraphy. However, only two of these cases showed metastatic spread by more conventional diagnostic techniques, including computer-assisted tomography, ultrasonography, and angiography. Successful tumor radiolocalization appeared to depend on tumor size, with lesions smaller than 2 cm in diameter not being detected. Tumors containing a CEA concentration above 115 ng/g, including a benign neoplasm, could be localized with radioactive anti-CEA antibodies. Administration of radioiodinated normal goat IgG to four patients with malignant or benign ovarian tumors failed to show tumor radioimmunodetection. One of these cases subsequently demonstrated a 4- x 4-cm tumor after receiving specific radiolabeled anti-CEA IgG. This study shows that ovarian neoplasms containing CEA can be detected and localized by external photoscanning after the application of radioiodinated antibodies to CEA and that, in this small series of patients, primary and secondary tumors could be detected in 100 and 67% of the cases, respectively.

Adenocarcinoma↗

Search for Epstein-Barr and type C oncornaviruses in systemic lupus erythematosus.

Lymphoblastoid cell lines were derived from patients with active systemic lupus erythematosus by allowing spontaneous transformation of peripheral B lymphocytes (B cells) harboring endogenous Epstein-Barr virus or by superinfecting peripheral lymphocytes with exogeneous Epstein-Barr virus. Results of extensive studies aimed at identifying type C oncornaviruses in these lymphoblastoid cells were entirely negative by electron microscopy, DNA-DNA hybridization, reverse transcriptase assays, and cocultivation experiments. These results do not support the postulated association of oncornavirus infection in human systemic erythematosus.

B-Lymphocytes↗

Use of radiolabeled antibodies to carcinoembryonic antigen for the detection and localization of diverse cancers by external photoscanning.

To determine whether tumors containing carcinoembryonic antigen could be detected by administration of a radiolabeled, affinity-purified, goat lgG having 70 per cent immunoreactivity against carcinoembryonic antigen, 18 patients with a history of cancer of diverse histopathology received an average total dose of 1.0 mCi of 131l-labeled lgG. Total-body photoscans were performed with a gamma scintillation camera at various intervals after administration of the radioactive antibody. Ordinary photoscans proved difficult to interpret because of blood-pool background radioactivity, thus necessitating the computer subtraction of radioactive blood-pool agents from the antibody's 131l activity. Tumor location could be demonstrated at 48 hours after injection in almost all cases studied. The scans were negative in patients without demonstrable tumors or with tumors apparently devoid of carcinoembryonic antigen. Circulating antigen levels of up to 350 ng per milliliter did not prevent successful tumor imaging after injection of the radioantibody.

Animals↗