A 64-year-old white male was referred for evaluation of prolonged prothrombin time (PT) and activated partial thromboplastin time (aPTT) obtained before elective surgery with initial PT and PTT results of 14.9 and 38.4 seconds, respectively, which corrected to normal in 1:1 mixes with normal plasma. Functional prothrombin assay indicated a level of 51% with thromboplastin as an activator. The prothrombin antigen was 102%. This discordance in the functional and immunologic prothrombin levels was evidence for dysprothrombinemia. Western blotting showed that thrombin was formed at a normal rate in diluted plasma consistent with a mutation within the thrombin portion of prothrombin. DNA was isolated from leukocytes and the thrombin exons were amplified by polymerase chain reaction, cloned, and sequenced. For exon 13, eight clones were sequenced with four clones showing a point mutation in the codon for Arg517, which would result in substitution by Gln. Arg517 is part of the Arg-Gly-Asp(RGD) sequence in thrombin and contributes to an ion cluster with aspartic acid residues 552 and 554. Mutation at this residue most probably distorts the structure of the Na+ binding site in thrombin. This is the first report indicating the critical role of Arg517 in the normal physiological interaction of thrombin with fibrinogen. This dysprothrombin is designated Prothrombin Greenville.

SUMMARYNine subjects with late onset unipolar depression were studied, before and after treatment, using 1-123 iodoamphetamine SPECT. In ail nine subjects clinical improvement was associated with a significant increase ( P~0 . 0 1 ) in cerebrallcerebellar activity ratios that correlated well with the decline in Hamilton depression scores.KEY woms-Depression, Elderly people, SPECT.Single photon emission computed tomography (SPECT) is a well-established and widely used in vivo method of studying neuronal function (Holman, 1986). SPECT, with flow tracers such as NIsopropyl Iodine-123-p-iodoamphetamine (IMP) and Technetium-99 hexamethylpropyleneamineoxime (Tc-99 HMPAO), has been used extensively to evaluate neuropsychiatric disorders (Holman, 1986). The results obtained from these SPECT studies closely parallel those obtained from positron emission tomography (Holman, 1986;Hunter et al., 1989). In the realm of neuropsychiatric disorders, relatively little attention has been devoted to SPECT studies of affective illness and schizophrenia (Hawton et al., 1990;O'Connell et al., 1989).Major depressive illness is one of the most common mental health problems in the elderly. It affects about 2-3% of individuals above the age of 60 (Alexopoulos, 1988). In about 3 M O % of these cases the depressive illness occurs de novo after the age of 60 (Alexopoulos, 1988). This disorder, commonly referred to as late onset depression (LOD), has certain unique clinical and pharmacologic features that suggest that it may represent a distinct clinical entity. Subjects with LOD have been shown to be more delusional, cognitively impaired, somatically preoccupied and more prone to relapses than subjects with an earlier onset of major depression (Alexopoulos, 1988).There have been no reports of physiologic studies in subjects with LOD either before or after successful treatment of depression. As part of a pilot study to examine the effects of successful somatic treatment of depression on neuronal function, we studied nine subjects with LOD before and after treatment of the depressive episode using SPECT with 1-123 IMP. METHODOur sample comprised nine subjects (five women and four men) mean age 72 f 3 who met DSM-III-R criteria for major depressive disorder-unipolar (Hamilton rating scale score for depression, mean f SD = 23 f 3) (HRSD). One subject was diagnosed as having major depression with moodcongruent psychotic features at the time of the initial scan. All subjects had their first episode of major depression after age 60 and were free of antidepressants for at least 72 hours prior to the scan. The subjects were inpatients on the psychiatry service at the Hospital of the University of Pennsylvania at the time of the study and were referred to this tertiary medical center for evaluationkreat-

A 64-year-old white male was referred for evaluation of prolonged prothrombin time (PT) and activated partial thromboplastin time (aPTT) obtained before elective surgery with initial PT and PTT results of 14.9 and 38.4 seconds, respectively, which corrected to normal in 1:1 mixes with normal plasma. Functional prothrombin assay indicated a level of 51% with thromboplastin as an activator. The prothrombin antigen was 102%. This discordance in the functional and immunologic prothrombin levels was evidence for dysprothrombinemia. Western blotting showed that thrombin was formed at a normal rate in diluted plasma consistent with a mutation within the thrombin portion of prothrombin. DNA was isolated from leukocytes and the thrombin exons were amplified by polymerase chain reaction, cloned, and sequenced. For exon 13, eight clones were sequenced with four clones showing a point mutation in the codon for Arg517, which would result in substitution by Gln. Arg517 is part of the Arg-Gly-Asp(RGD) sequence in thrombin and contributes to an ion cluster with aspartic acid residues 552 and 554. Mutation at this residue most probably distorts the structure of the Na+ binding site in thrombin. This is the first report indicating the critical role of Arg517 in the normal physiological interaction of thrombin with fibrinogen. This dysprothrombin is designated Prothrombin Greenville.