This vaccine worked, and for some years after it was used by people in that region to convert the illness from one with high fatality rate (albeit low incidence) to one that could be either prevented entirely (for many of them) or modified to a non-deadly form (for the rest). Today there is no commercially available vaccine for RMSF because, unlike in the 1920s when Spencer and colleagues developed one, antibiotics are now available to treat the disease, so prevention by vaccination is no longer the sole defense against likely death. Much of the early research was conducted at Rocky Mountain Laboratories a part of the National Institute of Allergy and Infectious Diseases. The schoolhouse laboratory of 1922–1924, filled with ticks in various phases of the life cycle, is identifiable in retrospect as a biohazard, although the team did not fully appreciate it at first. The deaths of Gettinger and Cowan, and the near death of the janitors son, were the results of inadequate biocontainment, but in the 1920s, the elaborate biocontainment systems of today had not been invented. Society
Research into this disease in Montana is a sub-plot of the 1937 film Green Light, starring Errol Flynn. Some of the researchers who perished are mentioned by name and their photographs are shown. Rocky Mountain spotted fever is a big part of the 1947 Republic Pictures movie Driftwood, starring Walter Brennan, James Bell, Dean Jagger, Natalie Wood, and Hobart Cavanaugh.
For this reason many of the antithrombin structures stored in the protein data bank and presented in this article show variable glycosylation patterns. Antithrombin begins in its native state, which has a higher free energy compared to the latent state, which it decays to on average after 3 days. The latent state has the same form as the activated state - that is, when it is inhibiting thrombin. As such it is a classic example of the utility of kinetic vs thermodynamic control of protein folding. Function
Antithrombin is a serpin (serine protease inhibitor) and is thus similar in structure to most other plasma protease inhibitors, such as alpha 1-antichymotrypsin, alpha 2-antiplasmin and Heparin cofactor II. The physiological target proteases of antithrombin are those of the contact activation pathway (formerly known as the intrinsic pathway), namely the activated forms of Factor X (Xa), Factor IX (IXa), Factor XI (XIa), Factor XII (XIIa) and, to a greater extent, Factor II (thrombin) (IIa), and also the activated form of Factor VII (VIIa) from the tissue factor pathway (formerly known as the extrinsic pathway). The inhibitor also inactivates kallikrein and plasmin, also involved in blood coagulation. However it inactivates certain other serine proteases that are not involved in coagulation such as trypsin and the C1s subunit of the enzyme C1 involved in the classical complement pathway.Protease inactivation results as a consequence of trapping the protease in an equimolar complex with antithrombin in which the active site of the protease enzyme is inaccessible to its usual substrate.