Recent studies indicated that the formation of a major constituent of Alzheimer's disease (AD) senile plaques, called BACpeptide, does not result from normal processing of its precursor, amyloid precursor protein (APP). Since protcolytic cleavage of APP inside its /?A4 sequence was found to be part of APP processing the formation of the PA4-peptide seems to be prevented under normal conditions. We considered whether in AD one of the endogenous proteinase inhibitors might interfere with APP proce s mg. After we had recently found that cultured human ncuronal cells s' synthesize the most potent of the known human proteinase inhibitors, a-t-macroglobulin (arZM), upon stimulation with the inflammatory mediator interleukin-6 (IL-6) we now investigated whether or2M and IL-6 could be detected in AD brains. Here we report that AD cortical senile plaques display strong u2M and IL-6 immunoreactivity while no such immunoreactivity was found in age-matched control brains. Strong perinuclear KIM immunoreactivity in hippocampal CA1 neurons of Alzheimer's discasc brains indicates that neuronal cells are the site of ~t2M synthesis in AD brains. We did not detect elevated IL-6 or or2M levels in the cerebrospinal fluid of AD patients. Our data indicate that a sequence of immunological events which seem to be restricted to the local cortical environment is part of AD pathology.

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The small bacteriochlorophyll-binding polypeptide of the light-harvesting complex B 870 was extracted from the intracytoplasmic membrane of the strain A1 a + of Rhodopseudomonas capsulata with chloroform/methanol/ammonium acetate and separated by chromatography on Sephadex LH60 using the same solvent. The polypeptide obtained from the peak fraction I11 was found to be homogeneous and identical with the small polypeptide isolated from the B 870 complex as shown by dodecyl sulfate/polyacrylamide gel electrophoresis, amino acid composition and N-terminal sequence. The complete amino acid sequence is given. The relative molecular mass based on the amino acid sequence is 5341. The polarity of amino acids is 35.42 %. The C-terminal part of the peptide chain from residue 29 to 48 is hydrophobic and includes one His residue.Rhodopseudomonas capsulata, an anoxygenic facultative phototrophic bacterium, produces ATP by cyclic photophosphorylation when grown anaerobically in the light [I]. The antenna pigments, i.e. bacteriochlorophyll a and carotenoids, are bound to hydrophobic membrane polypeptides [2 -61. The non-covalent polypeptide-pigment association effects a shift of the red absorption band of bacteriochlorophyll to longer wavelength from 770nm to 800nm, 850nm and 870nm. It causes an orientation of the pigment molecules relative to the plane of the membrane and a spatial arrangement of antenna-pigment complexes around reaction centers in order to optimize energy transfer from the B800-850 complex to photochemical reaction centers via B870 complexes [7] (and J. Peters, J. Takemoto, G. Drews, unpublished). It is open to discussion wheter the pigment-binding polypeptides have an additional function in energy transfer.In order to understand molecular organization and function of pigment complexes, we investigated the primary structure of pigment-binding polypeptides and neighborhood relationships between the polypeptides in the membrane [3 -6,8].The light-harvesting complex I (B870) contains two bacteriochlorophyll-binding polypeptides of apparent M , 12000 and 7000 [4]. In this paper the isolated and complete amino acid sequence of the small polypeptide of this complex is described. MATERIALS AND METHODS Cell material, isolation of membranesIntracytoplasmic membranes were isolated from anaerobically light-grown cells of the strain Ala' of Rhodopseudomonas capsulata (crt-, pho', B800 -850-) as described [2,3]. Isolation of polypeptidesThe polypeptides of the light-harvesting complex I were extracted from 80 mg freeze-dried intracytoplasmic membranes or 8 mg freeze-dried complex I with 4 ml and 2 ml, respectively, chloroform/methanol (1 : 1 ; v/v) mixture containing 0.1 M ammonium acetate.The extract was centrifuged (IOmin, 1OOOxg) and the supernatant decanted. The pellet was reextracted with 2 ml of the same solvent. 4.5ml of the combined supernatants were applied to chromatography on a Sephadex LH60 (Pharmacia) column (2.6 x 98 cm) and eluted at 10 "C with the same solvent as described [5]. Polyacrylamide gel electroph...

Plasma protein C exerts anticoagulatory effects by inactivating factors V and VIII. Hereditary protein C deficiency is transmitted as an autosomal dominant disorder. Homozygous individuals usually develop purpura fulminans as newborns; heterozygous protein C-deficient individuals are at increased risk for venous thrombosis and pulmonary embolism. However, arterial thrombosis has been only rarely observed. We describe a young patient with heterozygous protein C deficiency who experienced a severe stroke due to thrombotic occlusion of the left middle cerebral artery. (Stroke 1990;21:1077-1080) P rotein C is a plasmaglycoprotein with a molecular weight of 62 kDa. Its synthesis by the liver depends on vitamin K. The inactive form of protein C is converted to the active protein C a by thrombin in the presence of Ca . Combination of thrombin with the cofactor thrombomodulin on the surface of endothelial cells greatly accelerates the activation rate of protein C.1 Protein C a acts as an anticoagulant by inactivating factors V a and VIII a . Protein C a also exerts profibrinolytic properties by inactivating plasminogen activator inhibitor 1. Protein S, which is also a vitamin K-dependent plasma protein synthesized by the liver and the endothelium, enhances the activity of protein Ca. 23Protein C deficiency is inherited as an autosomal dominant trait with incomplete penetrance. Heterozygous individuals have an increased risk of venous thrombosis and thromboembolism at a young age. 4 Homozygous protein C deficiency is rare and leads to a purpura fulminans-like syndrome in neonates. Homozygous individuals usually die within the first months of life unless treated with replacement of protein C during the acute phase, followed by lifelong anticoagulation. 55 Two types of protein C deficiency are known. Most common is type I, in which both the absolute concentration of protein C and its functional activity are reduced. In type II protein C deficiency the activity is reduced whereas the concentration of protein C is normal. 3 We describe a young patient with heterozygous protein C deficiency. Occlusion of the left middle cerebral artery led to a severe ischemic stroke. Received December 11, 1989; accepted February 28, 1990. Case ReportAfter suffering from a headache for several days, a 32-year-old mechanic acutely developed a brachiofacial hemiparesis of his right side and global aphasia. Cranial computed tomography showed an extensive ischemic infarct in the territory of the left middle cerebral artery (Figure 1). Occlusion of the left middle cerebral artery at its proximal stem was demonstrated by transtemporal Doppler sonography (Figure 2). Duplex scanning of the extracranial carotid arteries did not show arteriosclerotic lesions but revealed reduced blood flow velocities on the left. Since the Doppler sonographic data were unequivocal, cerebral angiography was not done.The patient had been healthy until this event, and there were no obvious precipitants of thrombosis (i.e., no trauma, intoxication, or dehydration). His on...