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The purpose of this paper is to report a pedigree with hereditary hemochromatosis in which a recombination between the HLA-A and B loci occurred. Both the maternal and paternal HLA-A3, B7 haplotypes were carrying an allele for hemochromatosis. The A3, B12 haplotype of the proband was a recombinant of the maternal A3, B7 and A28, B12 haplotypes. The hemochromatosis locus segregated with the HLA-A locus and not with the HLA-B locus. Thus, the hemochromatosis locus maps in close proximity to the HLA-A locus.

The synthetic terpolymer L-glutamic acid60-L-alanine30-L-tyrosine10 (GAT) stimulates GAT-specific suppressor T cells in nonresponder mice. Extracts from these T cells contain a GAT-specific soluble T cell suppressor factor (GAT-TsF) that inhibits development of GAT-specific plaque-forming cell (PFC) responses by spleen cells from nonresponder mice stimulated with GAT complexed to methylated bovine serum albumin (GAT-MBSA). These extracts also contain a factor that inhibits development of GAT-specific proliferative responses by GAT-MBSA-primed, nonresponder lymph node T cells. Experiments reported in this manuscript show that a hybrid T cell line, produced by fusion of the AKR thymoma, BW5147, with spleen cells that contain GAT-specific suppressor T cells, produces a constitutive GAT-specific suppresor factor that functionally and serologically resembles GAT-TsF extracted from T cells. More importantly, both GAT-specific PFC and T cell proliferative responses are inhibited by this factor.

Antithrombin-III (AT-III) and factor VIII coagulant (F VIII:C) and antigenic (F VIII:RA) activities have been studied in nine conservatively treated and 26 dialysed uraemic patients. AT-III levels were not significantly different from those of controls in either group. Among dialysed patients, those who had experienced thrombotic occlusions of the vascular accesses could not be distinguished from the remaining patients on the basis of their AT-III levels. Both F VIII:C and F VIII:RA were slightly higher than in controls in conservatively treated patients, but significantly higher in haemodialysed patients, especially in those who had never experienced thrombotic complications of the vascular accesses. No acute changes were observed in either the AT-III or F VIII:C/F VIII:RA ratio in five patients given heparin therapy during a dialytic session or in the interdialytic period. Thus repeated intermittent heparin treatment does not induce a hypercoagulable state in haemodialysed patients.

The authors have tried to determine which patients were at risk of venous thrombosis. They chose 10 tests for hemostasis that might be of value in predicting those patients who were at risk. The tests were used in two groups of patients: one group in a respiratory intensive care unit and another group of patients about to undergo a major spinal operation. The tests were those for measuring: platelet count, prothrombin time, activated partial thromboplastin time, platelet thromboplastic activity (platelet factor 3), plasma clotting time, and concentrations of fibrinogen, plasminogen, antithrombin-III, alpha-1-antitrypsin and platelet fibrin degradation products (FDP). A diagnosis of thrombosis was made by three techniques: radioactive fibrinogen accumulation in the developing thrombus, impedance plethysmograhpy and ascending venography. The only test for hemostasis that discriminated between patients with and without thrombosis was the level of circulatory FDP. Several of the tests showed pronounced changes within the normal range following development of thrombosis and even before its detection. Therefore, none of the tests was truly predictive. A detailed discussion of the performance and interpretation of impedance plethysmography is presented.

Three laboratory methods for monitoring heparin treatment have been compared using 63 plasma samples: the thrombin time, the activated partial thromboplastin time, and the measurement of the heparin concentration using a chromogenic substrate. A good correlation was found between the methods. However, the intensity of anticoagulation was identical in only 27 of the 63 samples (43%) when the thrombin time and the activated partial thromboplastin time were compared. Fully discordant results were recorded for four samples (6%). The thrombin time was found to be more closely related to the plasma heparin concentration than was the activated partial thromboplastin time. Both antithrombin-III activity and immunologic levels were lower in the group with strong heparinization. It is suggested that the thrombin time is a good and safe method for monitoring heparin treatment.

5'Mercaptouridine-5'-diphosphate (hs5UDP) has been synthesized and investigated as a substrate of the polynucleotide phosphorylase of Micrococcus luteus. While hs5UDP is not utilized alone, it can be copolymerized with UDP; however, unusually for this enzyme, the ratio of 5'mercaptouridylate vs. uridylate residues in the polynucleotide product (MPU) is always lower than the ratio of hs5UDP v. UDP in the substrate mixture. Furthermore, hs5UDP decreases the rate of the enzymic polymerization reaction. The MPU product forms two-stranded and three-stranded complexes with poly(A). The circular dichroic spectra of these complexes are similar to those formed between poly(U) and poly(A), but their melting profiles indicate somewhat lower stability. The physicochemical and biochemical properties of the enzymic product are qualitatively similar to those of MPU prepared by chemical modification; both are potent inhibitors of a DNA-dependent RNA polymerase.

Two siblings, suffering from recurrent thrombosis and protein-losing enteropathy are presented. Histopathological examination of the liver in one of the patients, who died of multiple thrombosis, showed changes characteristic of Congenital Hepatic Fibrosis. Coagulation studies in the second child revealed decreased antithrombin-III in plasma, which might have had pathogenetic implications for the thrombosis tendency seen in both patients.