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By using the intra-I region recombinant mouse strain B10.ASR7 (H-2as3), the immune response (Ir) genes for LDH-B and MOPC-173 were genetically and serologically separated, as assayed by T cell proliferation. Previous work demonstrated that H-2s and H-2b strains respond to LDH-B and MOPC-173 whereas H-2a and H-2k strains failed to respond due to haplotype-specific suppression of I-Ak molecule-activated T helper cells by I-Ek molecule-activated T suppressor cells. In the experiments reported here, B10.ASR7 mice, which lack I-Ek expression, mounted a significant T cell proliferative response to LDH-B but not to MOPC-173. Separation of the Ia determinants used in restricting these two antigen responses was further confirmed when pretreatment of B10.S(9R) (A beta sA alpha sE beta sE alpha k) macrophages with A.TL anti-B10.HTT serum (anti-As beta Es beta Js) adsorbed with B10.ASR7 spleen cells blocked the MOPC-173 response but not the LDH-B response. Unadsorbed serum blocked both antigen responses. The B10.ASR7 E beta allele was determined to be s due to the ability of (A.TL X B10.ASR7)F1 hybrids to mount a T cell proliferative response to the terpolymer GLPhe. Monoclonal antibody blocking of the B10.ASR7 T cell proliferative response to LDH-B demonstrated that the Ia.2 and Ia.17, and not the Ia.15 epitopes are spatially related to the Ia epitopes involved in the restriction of the B10.ASR7 LDH-B T cell proliferative response. In addition, B10.ASR7 helper T cells generated in response to LDH-B were suppressed in a haplotype-specific manner by I-Ek molecule-restricted suppressor T cells in that (A.TL X B10.ASR7)F1 hybrids failed to respond to LDH-B. This nonresponsiveness was eliminated by treatment with monoclonal antibodies directed against the I-Ek molecule. These results suggest the possibility that the immune response defect in B10.ASR7 could be related to the site of recombination.

A recirculating perfused rabbit heart preparation is used to study the reaction of antithrombin III (ATIII) with thrombin bound to the surface of the microvascular endothelium. Addition of ATIII to the system after thrombin is equilibrated with its binding sites results in inhibition of the enzyme as measured by disappearance of thrombin enzymatic activity from the circulation or by appearance of 125I-thrombin-ATIII complexes. The rate of inhibition of thrombin as reflected by either method is independent of the bound state of thrombin. Comparable results are obtained with ATIII modified at a single tryptophan residue. This modification does not alter the reaction rate of ATIII with thrombin but abolishes the capacity of heparin or heparan sulfate to enhance the reaction rate. From the kinetics and structural studies and the fit of the kinetics to a theoretical model relating binding equilibrium to thrombin inhibition, it is concluded that glycosaminoglycans are not involved in the reversible, high affinity, high capacity binding of thrombin to the vascular endothelium.

In seven patients with hemochromatosis, arthropathy was an early symptom, or first clinical symptom, of the hemochromatosis. In all seven patients, serum iron, transferrin saturation, and parameters of storage iron (serum ferritin, Desferal-test) were clearly elevated. In 5 patients hemochromatosis was associated with the HLA loci A3 and B7. Bone scan proved a sensitive detection method for hemochromatosis arthropathy. In one case joint involvement was detected by bone scan prior to clinical symptoms. Parameters of iron metabolism correlated well with other organ manifestations of hemochromatosis. In contrast, joint involvement did not correlate with parameters of iron metabolism or severity of hemosiderosis of other organs, and was not relieved by phlebotomy. These 7 cases confirm that joint symptoms can be an early or leading symptom of hemochromatosis, can lead to early therapy and thereby prevent major organ damage. It remains undecided, however, whether the arthropathy is a consequence of iron storage or an independent disease which is genetically associated with hemochromatosis.

The paper presents two cases in which clinical and laboratory investigations have revealed the simultaneous presence of porphyria cutanea tarda (PCT) and adrenocortical insufficiency (ACI). Whether this association is a coincidence, whether there is a common cause, or a "cause to effect" type relationship between the two entities is a question of debate. Without ignoring other possible causes (tuberculosis, hemochromatosis, autoimmunity, drugs) it is suggested that heme deficit consequent to inefficient protoporphyrin synthesis results in impaired steroidogenesis, due to decreased levels of adrenocortical hemoprotein enzymes, especially cytochrome P-450 dependent hydroxylases. Cytochrome P-450 has a well known sine-qua-non activity in steroid hydroxylations within steroid tissues, and a decrease in the levels of this heme-enzyme might be expected to result in impaired steroidogenesis. However, the association between PCT and ACI (whether pathogenic or not) is pathophysiologically characterized by the coexistence of a disease (PCT) in which the anatomo-clinical manifestations are determined by oxygen derived free radicals ( ODFR ), and a disease (ACI) which, among other consequences, presents a marked reduction in ODFR -scavenge capacity. The authors consider this supposition an attractive working hypothesis, suitable to further clinical laboratory direct testing.