Masaru Koma

Remodeling of the Major Pig Xenoantigen by N-Acetylglucosaminyltransferase III in Transgenic Pig

We have been successful in generating several lines of transgenic mice and pigs that contain the human β-d-mannoside β-1,4-N-acetylglucosaminyltransferase III (GnT-III) gene. The overexpression of the GnT-III gene in mice and pigs reduced their antigenicity to human natural antibodies, especially the Galα1–3Galβ1–4GlcNAc-R, as evidenced by immunohistochemical analysis. Endothelial cell studies from the GnT-III transgenic pigs also revealed a significant down-regulation in antigenicity, including Hanganutziu-Deicher antigen, and dramatic reductions in both the complement- and natural killer cell-mediated pig cell lyses. Changes in the enzymatic activities of other glycosyltransferases, such as α1,3-galactosyltransferase, GnT-IV, and GnT-V, did not support cross-talk between GnT-III and these enzymes in the transgenic animals. In addition, we demonstrated the effect of GnT-III in down-regulating the xenoantigen of pig heart grafts, using a pig to cynomolgus monkey transplantation model, suggesting that this approach may be useful in clinical xenotransplantation in the future.

Reduction of the Major Swine Xenoantigen, the α-Galactosyl Epitope by Transfection of the α2,3-Sialyltransferase Gene

α2,3-Sialyltransferase represents a putative enzyme that reduces the Galα1-3Gal β1-4GlcNAc-R (the α-galactosyl epitope) by intracellular competition with α1,3-galactosyltransferase for a common acceptor substrate. This study demonstrates that the overexpression of the α2,3-sialyltransferase gene suppresses the antigenicity of swine endothelial cells to human natural antibodies by 77% relative to control cells and by 30% relative to cells transfected with α1,2-fucosyltransferase, and in addition, it reduces the complement-mediated cell lysis by 75% compared with control cells and by 22% compared with cells transfected with α1,2-fucosyltransferase. The mechanism by which the α-galactosyl epitope was reduced was also studied. Suppression of α1,3-galactosyltransferase activity by 30–63% was observed in the transfectants with α2,3-sialyltransferase, and mRNA expression of the α1,3-galactosyltransferase gene was reduced as well. The data suggest that the α2,3-sialyltransferase effectively reduced the α-galactosyl epitope as well as or better than the α1,2-fucosyltransferase did and that the reduction of the α-galactosyl epitope is due not only to substrate competition but also to an overall reduction of endogenous α1,3-galactosyltransferase enzyme activity.

Carcinosarcoma of the gallbladder producing α-fetoprotein and manifesting as leukocytosis with elevated serum granulocyte colony-stimulating factor: Report of a case

A 69-year-old man was referred to our hospital for investigation of leukocytosis and a persistent fever of 38°C, but we could find no evidence of a specific infection. The leukocyte count was 18 000/mm3, and the serum granulocyte colony-stimulating factor (G-CSF) and α-fetoprotein (AFP) levels were both elevated, at 66.3 pg/ml and 1,495 ng/ml, respectively. Computed tomography (CT) showed a gallbladder tumor and we performed extended cholecystectomy. Postoperatively, the fever subsided and the leukocyte count, serum G-CSF and AFP level normalized. Histologically, the tumor was a carcinosarcoma of the gallbladder. Immunohistochemical staining of the tumor cells was positive for AFP, but negative for G-CSF. This is the first report of a carcinosarcoma of the gallbladder producing AFP. The laboratory findings and clinical course strongly suggested that the tumor produced not only AFP, but also G-CSF.

Huge thymoma: role of preoperative WHO histological classification

A 57-year-old woman was admitted to our hospital with complaints of recent onset of dyspnea on exertion. A chest computed tomography revealed a large mediastinal mass which extrinsically compressed the heart and mediastinal structures, occupying one half of the hemithorax. A needle biopsy was performed to find a thymoma with type AB according to the WHO classification. Based on the radiological and histological finding a surgery for the tumor was achieved by exploratory VATS thoracotomy followed by thymectomy through a median sternotomy with tumor extirpation of 910 g in weight. A definite diagnosis of thymoma (Masaoka I) without capsular invasion was obtained from the pathologic findings, including positive immunohistochemical staining for CD1a and cytokeratin.

Clinical impact of concomitant surgical diagnosis and subsequent lobectomy for preoperatively undiagnosed lung cancer

OBJECTIVES We conducted a retrospective study of the clinical impact of a concomitant diagnostic and therapeutic procedure for patients with histologically unproven pulmonary nodules. METHODS Between January 2001 and December 2003, we performed 150 consecutive surgical biopsy procedures for histologically indeterminate pulmonary nodules. We compared the clinical impact of the concomitant diagnostic wedge resection followed by lobectomy (U group, n=50) with that of a scheduled standard lobectomy in those with preoperatively proven clinical stage I lung cancer during the same period (C group, n=60). RESULTS There were no significant differences in dichotomous variables, whereas we found significant differences in tumor size, operative time and blood loss between the 2 groups. Complication developed in 9 in the U group and 3 in the C group (p=0.030). Hospital mortality was 2% in the U group and 0% in the C group (p=0.11). CONCLUSION Morbidity and mortality following a concomitant diagnostic and therapeutic procedure in patients with preoperatively undiagnosed lung cancer was acceptable, however, staged operations should be indicated for patients with considerable co-morbidity.