Identification of Novel Human Cryogen and the Mechanism of Hypothermia

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We experienced a hypothermic patient, i.e., a young female who suffered from severe hypothermia in a cool environment. Although various medical and physiological tests were performed, we failed to end any abnormalities responsible for hypothermia. According to thermoregulatory function tests, it appears that the threshold core temperatures for cold-defense responses of the patient shifted to extremely low levels. When the patient's serum was injected into the peritoneal cavity of rats, profound hypothermia was induced. Thus, we speculated that there were yet unidentified cryogenic substance(s) in the patient serum, and hence attempted to identify the substance(s). The patient's serum was divided into 4 fractions according to their molecular sizes, i.e., below 10kDa, 10〜30kDa, 30〜100kDa and more than 100kDa, using various types of filtration tubes and membranes. The intraperitoneal injections of the third fraction (30〜100kDa) produced clear hypothermia in rats, while the other fractions did not. Since the fraction includes a large amount of serum albumin, we separated patients' serum into two fractions, albumin rich and free fractions, with a commercial column for affinity chromatography. when albumin rich fraction was injected into rats, it produced significant hypothermia. Gel electrophoresis of the albumin rich fraction showed the presence of bands which were not seen in the serum of healthy controls. In a preliminary study, one of the bands was taken and directly analyzed by mass spectrometry. According to the search of human genome database, a fragment of certain protein was included in the band. It was speculated that the patient may have produced, unknown cryogenic substance(s) which might be degradation products from serum proteins physiologically existing in human serum.