Modulation of growth and differentiation of human colon carcinoma cells by histone deacetylase inhibitory trichostatins

Histone deacetylase inhibitors such as sodium butyrate or (R)-trichostatin A {(R)-TSA; 7- [4-(dimethylamino) phenyl]-N-hydroxy-4,6-dimethyl-7-oxo-2, 4-heptadienamide} have been reported to modulate the proliferation and differentiation of certain cell types. In this study, we analyzed the effects of these agents on KM12 human colon carcinoma (HCC) cells in culture. We found that (R)-TSA induced cell flattening, inhibited anchorage-dependent and anchorage-independent growth, increased the level of the differentiation marker carcinoembryonic antigen, and increased the expression of gelsolin, a candidate tumor suppressor, in these HCC cells. Cells treated with (R)-TSA for 3 h exhibited a high degree of histone (primarily H4) acetylation. (R)-TSA exerted these effects at concentrations in the range between 0.1 to 1 mu M that are at least 1,000 times lower than those required to achieve similar effects by n-butyrate. Trichostatin C, which exhibits some histone deacetylase inhibitory activity but not the analogs (S)-TSA or (R)- or (S)-trichostatic acid, which lack histone deacetylase inhibitory activity, also showed some growth inhibitory activity. These results indicate that histone deacetylase inhibitors may lead to suppression of the transformed phenotype and enhanced differentiation in the KM12 HCC cells.     

Coagula tamponade as a complication of open heart surgery: the clinical significance and diagnostic value of transesophageal echocardiography]

The pathogenesis of low cardiac output failure (LOF) immediately after open heart surgery was studied in 41 patients with LOF and 15 control patients without LOF using echocardiography. In 35 patients, transesophageal echocardiography was also performed. Left ventricular (LV) contraction was impaired in 28 of the 41 LOF patients, in whom LV fractional shortening was less than 25%. In the other 13 LOF patients, however, it was greater than 25%. In 12 of these 13 patients, transesophageal echocardiography revealed that accumulating pericardial coagula were localized in the right side of the heart, deforming the right atrial and ventricular chambers. The LV end-diastolic diameter was significantly less than the control, indicating that the pericardial coagula disrupted the distension of the heart. Emergent coagulotomy was performed in 5 patients, and hemodynamic conditions were improved. In spite of "cardiac tamponade", the wall motion and pressure tracings of the right atrium and right ventricle in these patients differed from those in fluid tamponade. Therefore, this condition should be designated "coagula tamponade." In the other 22 patients in whom transesophageal echocardiography was employed, no coagula were observed. Since pericardial coagula can hardly be detected by transthoracic echocardiography, transesophageal echocardiography is indispensable for diagnosing pericardial coagula noted immediately after open heart surgery.     

Motion analysis in two dimensions of radial-ulnar deviation of type I versus type II lunates

The motions of 2 different types of lunate (type I, no medial hamate facet; type II, medial hamate facet) were evaluated and compared during radial-ulnar deviation of the wrist using radiography and magnetic resonance imaging. Ten right wrists (5 type I and 5 type II lunates) were studied using posteroanterior and lateral x-rays. Six of the 10 normal volunteers (3 type I and 3 type II lunates) were studied using magnetic resonance imaging in 6 positions of radial-ulnar deviation. In the radiographic study the ulnar shift ratio of the lunate (USR), the shortest distance between the proximal ulnar tip of the lunate and the distal ulnar edge of the sigmoid notch of the radius (R-L), the closest distance between the distal ulnar tip of the lunate and the proximal pole of the hamate (L-H), the radius of curvature of the proximal head of the capitate (Cr) on posteroanterior view, and the radiolunate angle on lateral view were measured in each wrist in each of the 6 positions. There were statistically significant differences between type I and II lunates with regard to average maximum ulnar deviation of USR and R-L, total change of USR, R-L distance and L-H distance, average L-H distance and Cr distance in all positions, and average radiolunate angle in neutral and 15 degrees ulnar deviation. In the magnetic resonance imaging study the wrists with a type I lunate did not have contact between the lunate and hamate in any position; the wrists with a type II lunate did have contact between the hamate and the lunate, but only in ulnar deviation. The results of this study demonstrate that the kinematics of a type I lunate are different from those of a type II lunate during radial-ulnar deviation of the wrist.     

Pathological analyses of early recurrence and malignant transformation in meningiomas

We investigated factors of the early recurrence and malignant transformation of histologically benign meningiomas using immunohistochemistry for MIB-1 positive indices (PI) and p53 protein expression, a flow cytometric DNA analysis, and the examination of numerical chromosomal aberrations detected by fluorescence in situ hybridization using an α-satellite DNA probe and abcr gene locus-specific probe. Twenty-six meningiomas of 23 patients were classified into two groups: the 3 patients in whom a recurrence was defined within two years after initial surgery and who showed histologically malignant features were classified as the early recurrent group, and the other 20 patients in whom recurrence did not develop during the same period were classified as the nonrecurrent group. DNA aneuploidy was observed in 40% of the nonrecurrent patients and in 67% of the early recurrent patients. Loss of chromosome 22 was the most common numerical aberration, but the aberrations characteristic of early recurrent meningiomas were not detected. The MIB-1 PI values of the early recurrent meningiomas were higher than those of nonrecurrent meningiomas, suggesting that MIB-1 PI is very important for biological and histopathological analyses and prediction of the future recurrence of meningiomas.     

A Case of Subcortical Meningioma

Subcortical meningioma, which has been reported as meningioma without dural attachment, a cerebral subcortical lesion, is extremely rare. Very few findings of radiological examination of subcortical meningioma have been described. Pre-operative differentiation of this lesion is generally difficult. We characterize the peritum oural oedema adjacent to the meningioma in this region, and we suggest that radiological findings of peritum oural oedema contribute to differential diagnosis of subcortical meningiomas.     

Left ventricular cardiac hemangioma in a patient with chronic heart failure

Cardiac hemangiomas are rare benign tumors. Here, we report the case of a man in his 30s who had a cardiac hemangioma with no symptoms. He was being treated with β-blockers for chronic heart failure with hypertensive heart disease at Osaka Minato Central Hospital. Routine echocardiography revealed a mobile spherical mass in the left ventricle that had not been detected on echocardiography performed 4 months previously. Subsequently, the tumor was excised to prevent potential embolic events and was pathologically diagnosed as a cardiac hemangioma. This case demonstrates the relatively rapid progress of a cardiac hemangioma regardless of β-blocker administration, which is occasionally used for the treatment of hemangiomas. The efficacy of β-blockers in treating cardiac hemangiomas may vary according to the type of β-blocker. Echocardiography is useful in screening and follow-up of cardiac hemangiomas; however, additional imaging modalities are needed for differential diagnosis.     

Numerical chromosomal abnormality in gastric MALT lymphoma and diffuse large B-cell lymphoma

Background: We investigated numerical chromosomal abnormalities, using the fluorescence in situ hybridization (FISH) method, in gastric mucosa-associated lymphoid tissue (MALT) lymphoma and diffuse large B-cell lymphoma (DLBL). We also compared the histopathological findings, including the presence or absence of Helicobacter pylori infection, with the analytical results. Methods: Sixteen patients who underwent operation for malignant gastric lymphoma in our department were divided into three groups: patients with low-grade gastric MALT lymphoma (l-MALT; n = 5), those with high-grade gastric MALT lymphoma (h-MALT; n = 8), and those with DLBL (n = 3). Numerical abnormalities of chromosomes 8, 9, 12, and 17 were investigated by the FISH method, and the presence or absence of H. pylori infection was microscopically examined. Results: Numerical abnormality was observed in chromosome 12 in 11 patients (68.8%), in chromosome 8 in 10 (62.5%), and in chromosome 17 in 5 (31.3%), showing a high frequency. H. pylori infection was detected in 80% and 50% of patients with l-MALT and h-MALT, respectively, but no H. pylori infection was observed in patients with DLBL. Conclusions: A new biological characteristic of gastric MALT lymphoma was obtained, i.e., a high frequency of numerical abnormalities of chromosomes 12, 8, and 17. There was no correlation between the numerical chromosomal abnormalities and the clinicopathological findings. Received: September 5, 2001 / Accepted: February 22, 2002 Acknowledgments. We sincerely appreciate the instruction and cooperation provided by Mr. A. Furuhata, Mr. S. Nakamura, and the staff, Department of Collaborative Pathology, Juntendo University, Tokyo, Japan. Reprint requests to: I. Watanobe