The organization of viral genes within the 3.7-kilobase-pair HindIII-KIEcoRI-S region of the Autographa californica nuclear polyhedrosis virus genome (85 to 88 map units) was determined by using a combination of nucleotide sequencing, transcriptional mapping, and in vitro translation of hybrid selected RNA. Two nonoverlapping genes, extending in opposite directions and encoding polypeptides with molecular weights of 35,000 and 94,000 (35K and 94K polypeptides), were identified. Unspliced, messenger-active RNAs were transcribed from both genes early (2 h) after infection. Indicative of immediate-early genes, transcription of the divergent RNAs was unaffected by the protein synthesis inhibitor, cycloheximide. Late in infection, abundant RNAs were transcribed from promoters located at least 2.5 kilobase pairs upstream from the gene encoding the 35K polypeptide. These transcripts completely overlapped both the 35K and 94K polypeptide genes but apparently lacked protein-coding potential, suggesting that the transcripts may play a role in the suppression of early viral gene expression.

Serum from a patient who died from massive hemorrhage within 4 months after onset of an acquired bleeding disorder at age 85 contained a potent inhibitor of fibrin stabilization. Other parameters of coagulation and fibrinolysis and his bleeding time were within normal limits.The inhibitor was shown to be an IgG with K light chains (IgG Kansas); its specific target was the factor XIII system itself. Although IgG Kansas combined with the virgin lab] form ofthe zymogen, it did not block the thrombin-catalyzed conversion to [a'b]. However, IgG Kansas prevented the subsequent Ca2+-mediated activation of [a'b] to a* + b, where a* denotes the catalytically competent factor XIIa species. IgG Kansas, in contrast to a previously studied autoimmune antibody from a similar bleeding disorder (IgG Warsaw), could also inhibit the transamidating activity of the preactivated a* enzyme.Autoimmune antibodies can cause the premature destruction ofcells or connective tissue constituents. Catastrophic bleeding may occur following the appearance ofantibodies capable of neutralizing one of the coagulation components in the circulation. In this latter category, investigations relating to inhibitors of the fibrin stabilizing factor (factor XIII) system are particularly challenging on account of the molecular complexity of the activation of the zymogen (1-3). Earlier reports (4, 5) described two patients with acquired antibodies specifically targeted against the thrombin and Ca2l-regulated conversion of factor XIII to the XIIIa enzyme, which is normally required to strengthen the fibrin clot by NE-(< glutamyl)lysine side-chain bridges (6). Nevertheless, the two inhibitors could be shown to differ from one another in terms of recognizing the a subunit of the zymogen, which carries the potential catalytic site. The present paper deals with yet another autoimmune inhibitor, which, like the previously studied examples, blocked the activation of factor XIII. However, it could be distinguished from them by virtue ofthe fact that it interfered also with the functioning of the factor XIII. enzyme. This antibody was identified in the plasma and serum of an elderly individual who died of massive hemorrhage. Case ReportAn 85-year-old white male retired farmer was admitted to the hospital for evaluation of a bleeding tendency. He Physical examination revealed dullness to percussion at the right lung base, and edema and tenderness of the right thigh. Hemoglobin was 11.0 g/dl; leukocytes, 6800 per sUI; and platelets, 548,000 per /1. Prothrombin time was 12.2 s (normal, 11.0-13.0 s); activated partial thromboplastin time, 28.7 s (normal, 24.0-38.0 s); fibrinogen, 533 mg/dl; and bleeding time, 5.5 min (normal, 2.5-9.5 min). A clot prepared from the patient's citrated plasma (recalcified by mixing equal parts of plasma and 0.025 M calcium chloride) dissolved in 5 M urea in <24 hr (7). Samples containing various concentrations ofpatient's plasma (ranging from 10% to 95%) were prepared by mixing patient's citrated plasma with citrated pooled norm...