Cellular actions and signaling by endostatin

The malignant transformation of a normal cell into a cancer cell requires no vasculature. Growth of solid tumors, however, requires angiogenesis to provide oxygen and nutrients to support cell proliferation. The switch from an avascular to a vascular phenotype is typically associated with acceleration of tumor growth. Antiangiogenic therapy, starving a tumor of its blood supply, is an attractive addition to the anticancer armamentarium. Animal tests of antiangiogenic therapy have shown remarkable potential. Initial human trials have proven antiangiogenic therapy to be remarkably nontoxic. Numerous antiangiogenic agents have been isolated as proteolytic fragments of endogenous polypeptides of the extracellular matrix. Endostatin was the first such antiangiogenic protein described and its potent antitumor effects in mice have generated wide interest. This review summarizes recent advances in endostatin biology and highlights new results on the cellular and subcellular mechanisms of endostatin action.     

Diagnostic significance of endocervical glandular cells with "golden-yellow" mucin on pap smear

Endocervical glandular cells rarely show "golden-yellow" mucin staining using the Papanicolaou technique, whereas the cells of adenoma malignum (minimal deviation adenocarcinoma) do. To further evaluate the significance of this finding, we reviewed the Pap smears of six cases in which atypical glandular cells containing golden-yellow mucin was identified. Microscopic examination of the hysterectomy specimens confirmed one case of adenoma malignum, whereas the other five cases were diagnosed as endocervical glandular hyperplasia with pyloric gland metaplasia. Glandular cells observed in all six cases were filled with golden-yellow mucin. In the case of adenoma malignum the nuclei were somewhat more enlarged and the chromatin texture was coarsely granular, although a distinction between adenoma malignum and the five benign lesions was difficult. Special staining performed on tissue sections in all cases demonstrated that the intracytoplasmic mucin of the glandular cells in portion of both pyloric gland metaplasia and adenoma malignum was predominantly PAS-positive and showed immunoreactivity for M-GGMC-1 (HIK1083), which reacts with pyloric gland mucin of the stomach. A review of 1,165 consecutive Pap smears failed to identify cells with golden-yellow mucin. These observations indicate that golden-yellow mucin on Papanicolaou smear seems to represent a gastric phenotype of endocervical glandular cells, which is a unique characteristic shared by adenoma malignum and pyloric gland metaplasia. This finding should therefore be regarded as a warning sign, raising the possibility of adenoma malignum and requiring prompt histopathologic assessment, although not of itself diagnostic of malignancy.     

Magnetically suspended centrifugal blood pump with a radial magnetic driver

A new magnetic bearing has been designed to achieve a low electronic power requirement and high stiffness. The magnetic bearing consists of 1) radial passive forces between the permanent magnet ring mounted inside the impeller rotor and the electromagnet core materials in the pump casing and 2) radial active forces generated by the electromagnets using the two gap sensor signals. The magnetic bearing was assembled into a centrifugal rotary blood pump (CRBP) driven with a radial, magnetic coupled driver. The impeller vane shape was designed based upon the computational fluid dynamic simulation. The diameter and height of the CRBP were 75 mm and 50 mm, respectively. The magnetic bearing system required the power of 1.0-1.4 W. The radial impeller movement was controlled to within +/- 10 microm. High stiffness in the noncontrolled axes, Z, phi, and theta, was obtained by the passive magnetic forces. The pump flow of 5 L/min against 100 mm Hg head pressure was obtained at 1,800 rpm with the electrical to hydraulic efficiency being greater than 15%. The Normalized Index of Hemolysis (NIH) of the magnetic bearing CRBP was one fifth of the BioPump BP-80 and one half of the NIKKISO HPM-15 after 4 hours. The newly designed magnetic bearing with two degrees of freedom control in combination with optimized impeller vane was successful in achieving an excellent hemolytic performance in comparison with the clinical centrifugal blood pumps.     

Foam cells generated by a combination of hyperglycemia and hyperlipemia in rats

Diabetes is a major risk factor for atherosclerosis, as well as hyperlipemia. Investigators have suggested that denatured lipoprotein in hyperglycemia transforms macrophages into foam cells, which correlates with the development or progression of atherosclerosis. In the present study, we examined the generation of foam cells in rats caused by a combination of hyperglycemia and hyperlipemia. Streptozotocin-induced diabetic male Wister rats were fed a high cholesterol diet (HCD) containing 1% cholesterol and 0.5% cholic acid to maintain a hyperglycemic and hyperlipemic state. Animals fed the HCD for 8 weeks or longer showed a high incidence of foam cell accumulation in the renal glomerulus, intima of aortic arch, splenic red pulp and marginal zone, liver sinusoid and intestinal lamina propria. The foam cells exhibited positive staining for antimonocyte/macrophage antibody and lipids in all these tissues. Anti-rat apolipoprotein B (apo B) antibody revealed that positive staining existed only in the cytoplasm of glomerular foam cells. These results suggest that the origin of these foam cells can be attributed to lipid-laden macrophages. The generation of foam cells in the hyperglycemia-hyperlipidemia supervening rat model presented in the present study might be a useful tool for investigations of the pathogenesis of foam cells.     

Clinical evaluation of the Gyro Pump C1E3 as a cardiopulmonary bypass pump

The Gyro Pump C1E3 is a new centrifugal pump with numerous features, including a ceramic pivot bearing system, secondary vanes, and an eccentric inlet port. To evaluate its biocompatibility, antithrombogenicity, and produced hemolysis, we used the Gyro Pump during cardiopulmonary bypass (CPB) for coronary artery bypass grafting (CABG) cases to compare it with the BioMedicus pump. From September 1998 to February 1999, 30 consecutive patients underwent CABG under conventional CPB. Fifteen patients were supported by the Gyro Pump C1E3 (Group G), and the remaining 15 patients, by a BioMedicus BP-80 pump (Group B). In both groups, flow rate was equivalent. Blood samples were taken as follows: preoperative, 60 minutes after the end of the procedure, and at postoperative days (POD) 0, 1, and 2. We evaluated the plasma free hemoglobin (free Hb) as an indication of hemolysis; beta-thromboglobulin (beta-TG) and platelet factor four (PF-4) as an indication of platelet deterioration; C3, C4, CH50 for complement activation; coagulation parameters, fibrinolytic factor, thrombomodulin, nitric oxide (NO), and endothelin as an indication of endothelial deterioration. This was the first clinical sized Gyro Pump CIE3. De-airing from the pump was easily accomplished via the eccentric oblique inlet port. The system, including its console, was easily and simply controlled. Perioperative laboratory data were not markedly changed in either group with demonstrated equivalence for biocompatibility and hemolysis. After pumping, no thrombus formation or pivot wear were observed inside the pump. This atraumatic, small centrifugal pump appears well suited not only for CPB but also for circulatory support.     

Primary Malignant Lymphoma of The Breast With a Review of 73 Cases among Japanese Subjects

We report a case of a 71-year-old female with primary malignant lymphoma of the breast. The patient noticed a lump in the right breast approximately six years prior to consultation to the Surgical Department because of a rapid growth of the lump, and had no other tumors noticed throughout the body during that period. Histology proved the case to be a “reticulum cell sarcoma” (large cell type) producing IgM in the tumor cells, idstead of a breast carcinoma as clinically diagnosed. At the same time, a total of 73 cases of mammary malignant lymphoma among Japanese subjects were reviewed. The criteria for primary or secondary malignant lymphoma of the breast, and histological diagnosis and pathogenesis of the primary breast malignant lymphoma were discussed.     

Endothelial Rho and Rho kinase regulate neutrophil migration via endothelial myosin light chain phosphorylation

The transendothelial migration of neutrophils is a critical step in acute inflammation, which we previously showed to be regulated by endothelial myosin light chain (MLC) kinase. Recent studies suggest that Rho and Rho kinase are also key mediators of MLC phosphorylation, but their roles in neutrophil migration have not been investigated. In the present study, a transwell chamber migration assay system incorporating endothelial monolayer was used to examine the numbers of migrating neutrophils, endothelial F-actin and myosin II rearrangement, and endothelial MLC phosphorylation at selected times during the neutrophil migration in vitro. The results showed that pretreating endothelial cells with C3 (Rho inhibitor) or Y-27632 (Rho kinase inhibitor) significantly diminished neutrophil migration, actin polymerization, myosin II filament formation, and MLC phosphorylation normally associated with the migration. These data suggest that endothelial Rho and Rho kinase regulate transendothelial neutrophil migration by modulating the cytoskeletal events that mediate such migration.     

Vesico-ileosigmoidal fistula caused by diverticulitis: report of a case and literature review in Japan

Enterovesical fistula is a relatively uncommon complication of colorectal and pelvic malignancies, diverticulitis, inflammatory bowel disease, radiotherapy, and trauma in Asian countries. A case of vesico-ileosigmoidal fistula and a literature review of this disease in Japan are presented. A 70-yr-old male was referred with complaints of urinary pain and pneumaturia. On admission, urinary tract infection and pneumaturia were presented. A barium enema demonstrated multiple diverticulum in his sigmoid colon and the passage of contrast medium into the bladder and ileum. Under the diagnosis of vesico-ileosigmoidal fistula due to suspected diverticulitis of the sigmoid colon, sigmoidectomy and partial resection of the ileum with partial cystectomy were performed. The histopathology revealed diverticulosis of the sigmoid colon with diverticulitis and development of a vesico-ileosigmoidal fistula. No malignant findings were observed. Until the year 2000, a total of 173 cases of vesico-sigmoidal fistula caused by diverticulitis had been reported in Japan. Pneumaturia and fecaluria are the most common types, presenting symptoms in 63% of the cases. Computed tomography, with a sensitivity of 40% to 100%, is the most commonly used diagnostic study. For patients with vesico-sigmoidal fistula, resection of the diseased sigmoid colon and partial cystectomy with primary anastomosis are the safest and most acceptable procedures, leading to the best results.