[Analysis of the Squamous Cell Carcinoma Antigen (SCCA) Which Has a Significant Difference in Values between CLIA and FEIA--Case Report of Extra Glycosylation in SCCA].

Squamous cell carcinoma antigen (SCCA) is a glycoprotein that belongs to the serine protease inhibitor family. Clinically, it has been utilized as a tumor marker for squamous cell carcinoma. In clinical laboratories, SCCA is measured by several immunoassays. Recently, a number of studies have been reported that there is a significant difference in values between the immunoassays, attributing to SCCA-immunoglobulin complex. We found a case with significant difference in the SCCA value between CLIA and FEIA. In this case, SCCA-Immunoglobulin complex was not confirmed by gel filtration analysis. Interestingly, 5 to 10 kDa slightly-high molecular weight SCCA compared to control was detected by immunoblotting assay. It may be suspected that the aberrant glycosyl modification of SCCA influenced the reactivity to immunoassays.

[An Abnormal Alpha-Fetoprotein Fractionation Provides Additional Information: A Case of Retroperitoneal Germ Cell Tumor Accompanied by Liver Cirrhosis Type C].

Most of germ cell tumor is gonadal origin. However 5% of malignant germ cell tumors appear in extragonadal organs. Because extragonadal germ cell tumors (EGGCTs) are found anywhere on the midline such as pineal gland, mediastinum and retroperitoneum, the origin of this type of tumor is controversial. EGGCTs are often seen between childhood and young adult; an elderly patient with EGGCT is rarely met. Here we report a case that an abnormal alpha-fetoprotein (AFP) fractionation pattern was helpful for diagnosis of retroperitoneal germ cell tumor. A presenile man with hepatic cirrhosis caused by chronic hepatitis C showed an intraperitoneal tumor-like mass on computed tomography and thus hepatocellular carcinoma was suspected. A serological test re- vealed elevated total AFP level and AFP-L3%. The latter is the proportion of fucosylated AFP on the lectin-affinity based fractionation. Noticeably the fractionation pattern of AFP of this patient was abnormal, sug- gesting a diversity of lectin-affinity of AFP in germ cell tumors. This patient also showed an atypical in- crease in beta human chorionic gonadotropin (8hCG). We suggest the measurement of 6hCG for early differ- ential diagnosis of retroperitoneal germ cell tumor and hepatocellular carcinoma when an abnormal AFP frac- tionation pattern was detected in a patient with suspected hepatocellular carcinoma. [Short Communication].

Systemic vasculitis associated with alphal-antitrypsin deficiency.

We describe a rare case of systemic vasculitis associated with alpha1-antitrypsin (alpha1-AT) deficiency. Mutational analysis of the alpha1-AT gene in this patient revealed a homozygous alpha1-AT Mnichinan variant. Alpha1-AT possesses broad-spectrum inhibitory activity against many serine proteases, including human neutrophil elastase, to help maintaining the crucial balance between proteases and protease inhibitors. The increase in free protease activity in the context of alpha1-AT deficiency may induce exacerbation of the vasculitis. This serious genetic defect severely affects the balance between a protease and a protease inhibitor at the pathological site.

Successful therapy with argatroban for superior mesenteric vein thrombosis in a patient with congenital antithrombin deficiency.

A 38-year-old woman was admitted with superior mesenteric vein (SMV) thrombosis, which was refractory to anticoagulation therapy. The plasma antithrombin activity was decreased and hardly compensated by concentrated antithrombin preparation due to high consumption rate. However, successful anticoagulation was achieved by administration of direct thrombin inhibitor, argatroban. Family studies of antithrombin activity revealed that she had type I congenital antithrombin deficiency. A novel heterozygous mutation in the gene for antithrombin (single nucleotide T insertion at 7916 and 7917, Glu 272 to stop in exon 4) was identified. Argatroban administration would be effective in the treatment of congenital antithrombin deficiency with SMV thrombosis.

A dominant negative form of the AAA ATPase SKD1/VPS4 impairs membrane trafficking out of endosomal/lysosomal compartments: class E vps phenotype in mammalian cells.

SKD1 is a member of the family of ATPases associated with cellular activities whose yeast homologue Vps4p has been implicated in endosomal/vacuolar membrane transports. When a mutant of SKD1 that lacks ATPase activity [SKD1(E235Q)] was overexpressed in mammalian cells, it induced a dominant negative phenotype characterized by aberrant endosomal structures (denoted as E235Q compartments). Expression of SKD1(E235Q) caused an accumulation of basolateral recycling receptors, such as asialoglycoprotein receptor and low-density lipoprotein in polarized hepatocytes and Madin-Darby canine kidney cells, respectively, in E235Q compartments. In addition, SKD1(E235Q) also abrogated, via endosomes, transport to the trans-Golgi network, as indicated by an accumulation of TGN38 in E235Q compartments. Three lines of evidence further demonstrated that SKD1 participates in the membrane transport from early endosomes to late endosomes/lysosomes: (1) a redistribution of a late endosomal and lysosomal membrane protein endolyn in E235Q compartments; (2) an inhibition of epidermal growth factor receptor degradation, due to an accumulation of the receptors in E235Q compartments; and (3) a mis-sorting of and defect in the proteolytic processing of newly synthesized cathepsin D. An intriguing finding was that the expression of SKD1(E235Q) caused the number of lysosomes to decrease (to one-sixth of control numbers) but their size to increase (2.4-fold larger in diameter than control lysosomes). Indeed, an ultrastructural analysis revealed that the expression of SKD1(E235Q) causes an accumulation of hybrid organelles formed by direct fusion between late endosomes and lysosomes. We conclude that SKD1 regulates multiple steps of membrane transport out of early endosomes and the reformation of lysosomes from a hybrid organelle.