Shirosaku Koide

Blood vessel invasion and expression of sialyl lewisx and proliferating cell nuclear antigen in stage I non‐small cell lung cancer. Relation to postoperative recurrence

Background. Recurrence in Stage I non‐small cell lung cancer was examined with respect to vascular invasion and the immunohistochemical expression of sialyldimeric Lewisx (SLX) and proliferating cell nuclear antigen (PCNA).

Evaluation of pericardial effusion with computed tomography.

Evaluation of pericardial effusion was attempted with computed tomography in 11 patients. The volume and distribution of pericardial fluid were assessed with satisfactory resolution and the nature of the fluid was estimated by the difference in x-ray transparency (CT numbers). The volume of pericardial fluid calculated by tomographic methods ranged from 25 ml. to 585 ml. and agreed well with the surgically drained fluid volume. The CT numbers of the pericardial effusion due to renal or heart failure, acute viral pericarditis, hypothyroidism, and hemopericardium were +12 to +13, +20, +28 to +30, and +26 to +40, respectively. Therefore the volume and gross nature of the pericardial fluid could be estimated noninvasively with computed tomography.

Biodegradable gelatin hydrogel potentiates the angiogenic effect of fibroblast growth factor 4 plasmid in rabbit hindlimb ischemia

OBJECTIVES We investigated the potentiation of gene therapy using fibroblast growth factor 4 (FGF4)-gene by combining plasmid deoxyribonucleic acid (DNA) with biodegradable gelatin hydrogel (GHG). BACKGROUND Virus vectors transfer genes efficiently but are biohazardous, whereas naked DNA is safer but less efficient. Deoxyribonucleic acid charges negatively; GHG has a positively charged structure and is biodegradable and implantable; FGF4 has an angiogenic ability. METHODS The GHG-DNA complex was injected into the hindlimb muscle (63 mice and 55 rabbits). Gene degradation was evaluated by using (125)I-labeled GHG-DNA complex in mice. Transfection efficiency was evaluated with reverse-transcription nested polymerase chain reaction and X-Gal histostaining. The therapeutic effects of GHG-FGF4-gene complex (GHG-FGF4) were evaluated in rabbits with hindlimb ischemia. RESULTS Gelatin hydrogel maintained plasmid in its structure, extending gene degradation temporally until 28 days after intramuscular delivery, and improving transfection efficiency. Four weeks after gene transfer, hindlimb muscle necrosis was ameliorated more markedly in the GHG-FGF4 group than in the naked FGF4-gene and GHG-beta-galactosidase (control) groups (p < 0.05, Kruskal-Wallis test). Synchrotron radiation microangiography (spatial resolution, 20 microm) and flow determination with microspheres confirmed significant vascular responsiveness to adenosine administration in the GHG-FGF4 group, but not in the naked FGF4-gene and the control. CONCLUSIONS The GHG-FGF4 complex promoted angiogenesis and blood flow regulation of the newly developed vessels possibly by extending gene degradation and improving transfection efficiency without the biohazard associated with viral vectors.

Effect of MCI-186 on postischemic reperfusion injury in isolated rat heart

MCI-186 (3-methyl-1-phenyl-2-pyrazolin-5-one) is a newly developed antioxidant which has been shown to reduce brain edema in cerebral ischemia through inhibition of the lipoxygenase pathway of arachidonic acid. However, its effect on myocardial reperfusion injury after prolonged ischemia has not yet been demonstrated. We compared the mode of the effect of MIC-186 and recombinant human CuZn superoxide dismutase (rh-SOD) in isolated perfused rat hearts subjected to 60-min ischemia followed by 60-min reperfusion. Left ventricular developed pressure (LVDP), necrotic area and the release of creatine phosphokinase (CPK) and endogenous CuZn superoxide dismutase (endoge-SOD) were measured to evaluate myocardial damage. The decrease in left coronary flow (CBF) was measured as an index of the damage of left coronary circulation. MCI-186 (14.5 mg/L) was perfused for 10 min in the MCI group and rh-SOD (70 mg/L) was perfused during the reperfusion period in the SOD group starting 5 min prior to reperfusion. The release patterns of CPK and endoge-SOD were analyzed to elucidate the difference in the mode of protection of MCI-186 and rh-SOD. The LVDP remained higher in both MCI and SOD groups than that of control (76 +/- 1, 77 +/- 2 and 69 +/- 1% of preischemic value, respectively). The necrotic area was significantly attenuated in both MCI and SOD groups compared with that in the control group (16 +/- 1, 14 +/- 1 and 32 +/- 1%, respectively, p < 0.05). Total CPK release was lower in both MCI and SOD groups than in the control (78 +/- 7, 100 +/- 2 and 116 +/- 4 x 10(3) units/g myocardium respectively). The decrease in CPK release was more marked in the MCI group than that in the SOD group (p < 0.05). The reduction in CBF was significantly attenuated by the treatment with rh-SOD or MCI-186, but the effect was much higher in the SOD group than in the MCI group (69 +/- 5, 58 +/- 2, and 48 +/- 2% in SOD, MCI and control groups, respectively). The release pattern of endoge-SOD was identical to that of CPK and thus this did not distinguish the mode of effect of MCI-186 from that of rh-SOD. These results indicate that MCI-186 reduces reperfusion injury in isolated perfused hearts with prolonged ischemia and the effect is more closely related to the reduction of myocyte damage than the preservation of the coronary circulation.

Glucose‐transporter‐type‐I‐gene amplification correlates with Sialyl‐Lewis‐X synthesis and proliferation in lung cancer

Increased glucose transport is a common characteristic of most tumors. To examine the role of elevated glucose uptake in lung cancer, we performed PCR amplification of 2 facilitative glucose transporter genes (GLUT1 and GLUT3) and immunohistochemical staining for GLUT1, proliferating cell nuclear antigen (PCNA), and sialyl Lewis × (sLex) on tumor specimens from 327 patients with lung cancer who underwent surgical resection from 1980 to 1993. To evaluate the relationship between GLUT, α‐2,3‐sialyltransferase (ST), and α‐1,3‐fucosyltransferase (Fuc‐T) genes, PCR amplification of the ST3N and Fuc‐TVII also was performed. Amplification of GLUT1 was significantly greater than that of GLUT3. GLUT1 and GLUT3 amplification correlated with PCNA staining (p < 0.01). In addition, GLUT1 amplification correlated with the grading of sLex staining as well as with the grading of GLUT1 staining (p < .03, p < 0.01). GLUT1 was co‐amplified with ST3N and Fuc‐TVII genes, which are involved in the synthesis of sLex (p < 0.01). The survival of patients whose tumors showed GLUT1 amplification was significantly shorter than that of patients whose tumors did not (p < 0.01). In a multivariate analysis of survival, GLUT1 remained a statistically significant prognostic factor. Our results suggest that GLUT1 amplification may participate in sLex synthesis as well as in proliferation, and may be of prognostic value in lung cancer. Int. J. Cancer74:189–192, 1997.

Evaluation of intracardiac thrombus with computed tomography

Left atrial (LA) and left ventricular (LV) thrombus was evaluated by computed tomography in 56 patients. The patients were divided into 2 groups: Group I, 28 patients with mitral valve disease, and Group II, 28 patients with myocardial infarction. Computed tomography and 2-dimensional echocardiography were performed in all the patients studied. Cineangiocardiography was performed in all Group I and in 13 Group II patients. Open heart surgery or autopsy was performed in all Group I and 4 Group II patients. The sensitivity in detecting LA thrombus was 100% with computed tomography, 70% with angiocardiography, and 60% with 2-dimensional echocardiography. The specificity in detecting LA thrombus was 91% with computed tomography, 86% with 2-dimensional echocardiography, and 88% with angiocardiography. Thrombi located at the LA appendage were associated with great difficulties in detection by other methods, but were well delineated with computed tomography. LV thrombus was also visualized by computed tomography with similar or greater accuracy than other diagnostic methods, although the sensitivity and specificity were not ascertained because surgery or autopsy was performed in only a minority of Group II patients. Therefore, as far as the detection of intracardiac thrombus is concerned, computed tomography has the advantage of offering uniform slices of the heart in an attempt to detect thrombi in unknown areas of cardiac chambers, including the LA appendage or LV apex, without being disturbed by the surrounding cardiac and noncardiac structures. Thus, computed tomography has excellent accuracy in the detection of intracardiac thrombus.

Endotracheal Tube with Movable Blocker to Prevent Aspiration of Intratracheal Bleeding

A newly developed endotracheal tube with a movable blocker was found to be lifesaving in patients with copious and persistent intratracheal bleeding. The cases of 4 patients are presented. In 3 patients, severe intratracheal bleeding was attributed to the extensive bronchopulmonary laceration caused by blunt chest trauma. In the remaining patient, the bleeding was due to rupture of the sutured site in the right pulmonary artery; the rupture was caused by a postoperative bronchopleural fistula. In these patients, spread of blood was completely prevented and pulmonary resection was performed safely by using the blocker in this new device.

α-2,3-Sialyltransferase type 3N and α-1,3-fucosyltransferase type VII are related to sialyl Lewisx synthesis and patient survival from lung carcinoma

Biosynthesis of sialyl Lewisx (sLex) requires a sialyltransferase for α‐2,3‐sialylation and a fucosyltransferase for α‐1,3‐fucosylation. To date, five human α‐1,3‐fucosyltransferase (Fuc‐T) genes and five human α‐2,3‐sialyltransferase (ST) genes have been cloned. However, it is not known which enzyme is mainly responsible for sLex synthesis.

Immunohistochemical study of glutathione-related enzymes and proliferative antigens in lung cancer. Relation to cisplatin sensitivity

Background. With resected tumor tissue from 84 patients with lung cancer, the expression of glutathione peroxidase (GPX), glutathione reductase (GR), proliferating cell nuclear antigen (PCNA), and epidermal growth factor receptor (EGFR) was examined in relation to cisdiamminedichloroplatinum (CDDP) sensitivity.

Evaluation of left atrial thrombus with computed tomography

Left atrial thrombi were evaluated with computed tomography in 23 patients with mitral valvular diseases. In three of the patients, left atrial thrombi were delineated with computed tomography and were confirmed by cardiac surgery or autopsy. The minimum size of the thrombi detected tomographically was 3.5 gm. There were no false-positive or false-negative results with computed tomography in 13 patients who subsequently underwent cardiac surgery. Computed tomography is essentially noninvasive and appears to be one of the best methods to evaluate left atrial thrombus.