Studies on the Level of Natural Antibodies Reactive with Various Tumor Cells during Urethane Carcinogenesis in BALB/c Mice

Serum from young normal BALB/c mice was found to contain IgM antibodies able tomediate complement-dependent lysis of certain syngeneic or allogeneic tumor target cells. The titer of such naturally occurring antitumor antibodies (NATA) was found to increase with aging.A longitudinal serological study comparing the cytotoxicity potential of NATA fromnormal and from urethan-treated BALB/c mice was performed. It was found that urethan-treated mice that did not develop primary lung-adenomas within the duration of the experi-ment had significantly lower NATA titers, against one out of 4 target cells assayed, than urethan-treated animals that developed lung adenomas. This difference was evident in two independent experiments. The results suggested that the lower NATA activity of the urethan-treated mice that did not develop tumors existed even before exposure to the carcinogenic insult. This raises the possibility that certain populations could be segregated according to their natural antibody profile into those individuals which will develop primary tumors within a certain period if exposed to a subthreshold amount of carcinogen, and those which will not.     

Monoclonal antibodies against human granulocytes and myeloid differentiation antigens

Monoclonal antibodies (MCA) were obtained by immunizing BALB/c mice with 99% pure granulocytes from normal donors or with a whole leukocyte suspension obtained from a chronic myelogenous leukemia (CML) patient, and then fusing the mouse spleen cells with a 315–43 myeloma cell clone. Four MCA were selected and studied using ELISA, immunofluorescence, cytotoxicity assays, and FACS analysis. Antibodies 80H.1. 80H.3. and 80H.5 (from normals) and 81H.1 (from CML) detected antigens expressed on neutrophils. Antibodies 80H.1 and 80H.3 (lgG) also reacted with monocytes but not with other blood cell subsets. Antibodies 80H.5 and 81H.1 (lgM) were cytotoxic and reacted strongly with most of the cells of the neutrophil maturation sequence. i.e., myeloblasts, promyelocytes, myelocytes, and mature granulocytes. Antibodies 80H.5 and 81H.1 also inhibited BFU-GM and CFU-E. Antigens recognized by 80H.3. 80H.5, and 81H.1 were expressed both on a proportion of cells from HL.60, KG.1, ML.1, and K562 myeloid cell lines, and on a proportion of blast cells isolated from patients with acute myelogenous leukemia. They were not found on lymphoid cell lines or lymphoid leukemia cells. These MCA recognize either late differentiation antigens expressed on mature neutrophils and monocytes (80H.1 and 80H.3) or early differentiation antigens (80H.5 and 81H.1) specific to the granulocytic lineage. They may be useful for a better definition of those antigens specific to hematopoietic stem cells and their relationship with normal or neoplastic hematopoiesis.     

The major histocompatibility complex (CyLA) of the cynomolgus monkey. I. Serologic definition of 21 specificities

Thirty-seven lymphocytotoxic antisera, 27 of which were raised by immunization with skin grafts and blood from partially matched donors, were tested against cells obtained from 218 unrelated animals and 205 offspring from a colony of cynomolgus monkey (Macaca fascicularis). Evidence was obtained for the presence of at least 21 specificities defined by cluster analysis and segregation within families. Allelic relationships between 16 specificities was suggested by segregation patterns, the absence of triplets and statistical analysis of association in the unrelated population sample. The data support a two-locus model, with tentative assignment of seven specificities to the A locus and six to the B locus. That these lymphocyte alloantigens constitute the major histocompatibility complex (MHC) of the cynomolgus monkey is suggested by analogy with other known MHCs and by the increased survival times of skin grafts between paternally matched half sibs compared to haplodistinct full sibs.     

改变在体兔左心室后负荷对其电生理参数的影响

目的：探讨改变在体兔左心室后负荷对室性心律失常发生情况及左心室电生理参数的影响。方法：改变左心室后负荷，观察室性心律失常发生情况，并测定左心室舒张阈值（ＶＤＴ），相对不应期（ＲＲＰ），有效不应期（ＥＲＰ）及其不应期离散和心室纤颤阈（ＶＦＴ）。结果：逐级增加左心室后负荷（ＡＢ级）可使左室空间ＲＲＰ，ＥＲＰ离散增加（Ｂ级，Ｐ＜００５），ＶＦＴ降低（Ｂ级，Ｐ＜００１）；各实验动物均出现室性心律失常（Ｂ级）；而逐级减小左室后负荷（ＣＤ级），心室电生理参数无变化（Ｐ＞００５），各实验动物亦无室性心律失常发生。结论：增加左心室后负荷诱发室性心律失常，与左室空间不应期离散增加有关。     

On the association between amyloid fibrils and glycosaminoglycans; possible interactive role of Ca2+ and amyloid P-component.

We have previously reported the specific association of glycosaminoglycans (GAG) and proteoglycans (PG) with amyloid fibrils and characterized the polysaccharides directly extracted from amyloid-laden tissues. In the present study we further elucidate the association between purified amyloid fibrils and GAG/PG with special reference to those GAG/PG associated with amyloid P-component (AP) and the interactive role of Ca2+ ions. Amyloid fibrils were isolated from human hepatic AA amyloid employing water extraction with and without preceding removal of AP, an extrafibrillar protein component of all amyloids, using sodium citrate. GAG/PG co-isolated with the amyloid extracts, with and without AP, were isolated and characterized. Agarose-affinity chromatography of extracts containing AP was performed, and the GAG associated with this extrafibrillary protein were characterized as well. Several different GAG/PG populations were demonstrated in the various extracts. The abolition of calcium-dependent binding markedly influenced the amount of GAG/PG recovered in the fibril extracts, as well as the total amount of amyloid material obtained. Thus, it seems that calcium plays an important role in the association between the fibrils and the sugar moieties, and that a significant fraction of the GAG found in amyloid exhibits a Ca(2+)-dependent fibril-GAG interaction. No significant difference in the proportion between galactosaminoglycans and glucosamines was, however, disclosed when the two extraction protocols were compared, suggesting that no particular GAG species has a higher affinity for the fibrils themselves. Both dermatan/chondroitin sulphate and heparan sulphate identified in the present study exhibited a Ca(2+)-dependent interaction with AP, supporting previous findings. However, the amyloid-associated galactosaminoglycans found, especially the large PG appearing in small amounts, seemed to have a higher affinity for the extrafibrillar AP than the other GAG.     

Response of body temperature and serum iron concentration to repeated pyrogen injection in rabbits

We measured body temperature and serum iron concentration after five daily consecutive injections of febrile doses of Salmonella typhosa lipopolysaccharide (0.1 g/kg) and two doses of Staphylococcus aureus cell walls (1×10⁷ and 5×10⁷ cells) in rabbits. Tolerance to endotoxin injection, as manifest by a significant attenuation in the body temperature elevation, developed after the first injection of endotoxin. The endotoxin-induced fall in serum iron concentration was attenuated significantly by the 5th day of endotoxin injection. In contrast, no tolerance developed in either the body temperature or serum iron response following repeated daily injections of S. aureus. Rabbits rendered tolerant to endotoxin showed normal febrile and serum iron responses to subsequent S. aureus injection. Rabbits given serial injections of S. aureus, although not tolerant to S. aureus itself, exhibited attenuated body temperature responses but not serum iron responses to endotoxin injection. We suggest that repeated injection of endotoxin diminishes the ability of endotoxin to stimulate endogenous pyrogen (EP) synthesis and/or release, a property not shared by the gram-positive pyrogen S. aureus. However, repeated injection of S. aureus weakens the central endotoxin-EP pathway.     

Genetic polymorphisms of orosomucoid and alpha-2-HS-glycoprotein in Thai,Sri Lankan and Paraguayan populations

The genetic polymorphism of orosomucoid (ORM) and alpha-2-HS-glycoprotein (AHSG) were studied in Thai, Sri Lankan and Paraguayan populations using isoelectric focusing. Gene frequencies in these populations were compared with those in other populations. Four new ORM variants were detected:ORM1 ^* 15 in Thai,ORM1 ^* 16 in Paraguayan,ORM2 ^* 21 andORM2 ^* 22 in Sri Lankan.     

Comparison of radioimmunoassay and ELISA methods for detection of antibodies to chromatin components

A solid phase radioimmunoassay has been compared with an enzyme-linked immunosorbent assay (ELISA) for efficacy in measuring anti-chromatin antibodies. The low backgrounds achieved with the radioimmunoassay method produced a high signal-to-noise ratio and enabled detection of the human test antiserum at a dilution of 1:102,400. By contrast, the ELISA could detect the same antiserum only at a dilution of 1:3200 and above. The radioimmunoassay was consistently more sensitive than the ELISA for detection of anti-chromatin antibodies in a number of human and mouse sera and ascites fluid containing a monoclonal antibody. Factors affecting sensitivity in both assays are discussed.     

An immunodominant haptenic epitope of carbamazepine detected in serum from patients given long-term treatment with carbamazepine without allergic reaction

An anticarbamazepine antibody was detected in the serum of a patient with severe carbamazepine-induced serum sickness. We found that the patient's T cells and IgG antibody recognized an epitope which appeared in subjects showing an allergic reaction, as well as that in subjects who showed no allergic reaction, after long-term carbamazepine therapy. These results show that an anti-carbamazepine immune response does not occur in the majority of subjects who undergo long-term carbamazepine therapy without developing allergic symptoms, although the immunodominant haptenic epitope of carbamazepine is present in their sera.