Gene Literature Dashboard

Highly significant suppression of the growth of S1509a and Sa-I syngeneic sarcomas was observed in A/J mice following daily intravenous injections of 2 microliter of anti-I-Jk alloantiserum. This effect persisted as long as the anti-I-Jk serum was administered (day 15), In contrast, a control anti-I-Js serum had no discernible effect on the growth of the S1509a tumor. The inhibitory activity of the anti-I-Jk serum on the growth of the tumor was absorbed specifically by B10-BR spleen cells bearing I-Jk determinants. In other experiments, we established that A/J mice treated with anti-I-Jk serum, according to the protocol described above, are no longer a source of tumor-specific suppressor cells for adoptive transfer into immune tumor-bearing recipient mice. We conclude that anti-I-Jk serum inhibits tumor growth in A/J mice by abolishing tumor-specific suppressor activity.

Partial amino acid sequence of the Ia molecule encoded by the I-E or I-C (I-EC) subregion of the major histocompatibility complex of the mouse are presented. The Ia molecule appears to be comprised of two noncovalently associated polypeptides. The larger subunit, alpha, has an approximate molecular weight of 35,000 and the smaller subunit, beta, an approximate molecular weight of 28,000. Several interesting homology relationships (or the lack thereof) are apparent when the Ia polypeptides from the I-EC subregion are compared both with their counterparts from man and guinea pig and with the molecules encoded in the I-A subregion. Clearly the most impressive homology relationship is that seen between the alpha polypeptide from the I-EC subregion of mouse and its human counterpart. This is in striking contrast to the beta polypeptide, which bears no apparent homology to its human counterpart.

An antiserum to methotrexate has been produced in a sheep against a conjugate of ovalbumin and methotrexate (MTX) prepared using a water-soluble carbodiimide. The antibodies produced were specific for substances containing the 2,4-diamino pteridine structure. Naturally occurring folates did not interfere with the assay. A radioimmunoassay has been developed using this antiserum, which can be used to measure MTX concentrations of less than 1 ng/ml in biological samples without prior extraction. The concentrations of MTX in the blood and urine of patients following a single i.v. bolus injection and following oral administration of the drug have been measured. The published radioimmunoassays for MTX have been compared.

Inactivation of alpha- and beta-thrombin by alpha 2-macroglobulin, by alpha 1-proteinase inhibitor and by antithrombin-III and heparin was studied. The amount of alpha- and beta-thrombin inactivated by antithrombin-III was proportional to the concentration of the inhibitor, but the inactivation rates of the two forms of thrombin were different. Heparin facilitated complex-formation between alpha-thrombin and antithrombin-III, whereas inactivation of beta-thrombin by antithrombin was only slightly influenced, even at a heparin concentration two orders of magnitude higher. alpha 2-Macroglobulin inhibited both alpha- and beta-thrombin activity similarly, i.e. the amount of alpha- and beta-thrombin inactivated as well as the rates of their inhibition were the same. alpha 1-Proteinase inhibitor also formed a complex with alpha- and beta-thrombin, similarly to antithrombin-III, although the inactivation of the enzyme needed high inhibitor concentration and long incubation time. These results suggest that the inactivation of beta-thrombin, if it occurs in the plasma, is also controlled by plasma inhibitors.

We studied iron overloading and HLA types in 24 sibships of patients with idiopathic hemochromatosis, of which 15 had at least two subjects with overt forms. HLA types of 84 unrelated patients were also investigated. Among siblings there was a significant association (P less than 0.0001) between the presence of hemochromatosis and the possession of the same two HLA haplotypes. The fact that overt forms of hemochromatosis depend on the presence of two specific homologous chromosomes strongly supports a recessive mode of transmission for the overt disease. The haplotypic equilibrium demonstrated in the unrelated patients group is another supporting argument. The lod-score value (2.239 for theta = 0.005) in six families available for study further supports the conclusion that a hemochromatosis gene is closely linked to the HLA-A locus. HLA typing in families with hemochromatosis could provide a means of early detection of subjects at risk before appearance of any sign of iron overload.

A 68-year-old man, after having been diagnosed as having hepatic disease at about the age of 41 years, had been hospitalized frequently until his death. Blood sugar, iron, and copper had not increased during his illness. Although the diagnosis of liver cirrhosis had been made and he had been receiving therapy, various neurologic symptoms without disturbances of consciousness appeared six months before his death. Autopsy revealed hemochromatosis, liver cirrhosis, and pancreatic fibrosis. A large amount of iron had accumulated in the liver, the pancreas, and the thyroid gland, while considerable numbers of ceroid and lipofuscin pigment granules had accumulated diffusely in the brain. Abnormal astrocytes of the Alzheimer II type were diffusely distributed in the brain and contained no intranuclear glycogen which stained positive with the carmine stain. No spongy changes were seen in the deeper layers of the cerebral cortex. Chemical analyses for trace metals in the brain, liver, and kidneys revealed a large amount of iron and increased copper in the liver, and considerable quantities of copper, manganese, calcium, and mercury in the brain. Because of changes in the erythrocyte sedimentation rate and marked thymol turbidity seen before and after the occurrence of the neurologic symptoms, this man was suspected of having disorders of the trace-metal binding proteins and/or of their polymers.