Induction of metallothionein synthesis by menadione or carbon tetrachloride is independent of free radical production.

The relationship between induction of hepatic metallothionein (MT) synthesis and lipid peroxidation by free radical production following an injection of menadione or carbon tetrachloride (CCl4) in mice was studied. The hepatic concentration of MT was increased by menadione significantly at 25 mg/kg or higher. A significant increase in thiobarbituric acid (TBA) value, indicative of lipid peroxidation, was observed in the liver at menadione doses of 62.5 mg/kg or higher. Both the MT and the TBA value in the liver were significantly increased at the low dose of CCl4. The concentration of MT was increased significantly 4-8 hr after administrations of these compounds. The increase of TBA value over time was similar to that of MT concentration after administration of CCl4, but not after administration of menadione. The MT concentration in the menadione group was higher than that in the CCl4 group, and the TBA level in the menadione group was lower than that in the CCl4 group. Pretreatment with vitamin E caused a significant reduction in the TBA value, but did not affect the MT level in the liver. The concentration of MT did not significantly correlate with the TBA value in either the menadione or the CCl4 group. Pretreatment with phenobarbital, which promotes free radical production, did not influence induction of MT synthesis following an injection of menadione or CCl4. Neither L-buthionine sulfoximine nor 2-cyclo-hexen-1-one, which decreases hepatic glutathione, influenced the induction of MT by menadione. These data suggest that induction of MT synthesis by menadione or CCl4 is independent of free radical production in the liver.     

Two cases of leiomyoma of the kidney]

Renal leiomyomas large enough to be clinically diagnosed are extremely rare. We review 30 cases of clinically diagnosed renal leiomyoma from the literature in Japan, including our 2 new cases. Case 1: In a 52-year-old man with no symptoms a renal mass was found accidentally on an ultrasonogram. CT scan showed a mass with a cystic area at the upper pole of the right kidney. Angiogram showed a hypovascular mass. Case 2: CT scan revealed a cystic mass and angiogram showed an avascular mass at the upper pole of the left kidney in a 19-year-old man having gross hematuria and left flank pain. Transperitoneal nephrectomy was done in both cases. Histologically each tumor was composed of monotonous proliferation of spindle shaped cells without atypia, which showed intense immunoreactivity for alpha-smooth muscle actin. The diagnosis of benign leiomyoma was made in each case. In a review of 30 cases, we found that renal leiomyomas occur most often in female (77%), between decades 2 and 5 of life (median: 46 years). On the angiogram it appears most often as an avascular or hypovascular mass. CT scan shows cystic or mixed solid/cystic or solid lesion, occasionally with calcification. Preoperative diagnosis is extremely difficult to be made. Histologically, fibroma, angiomyolipoma, congenital mesoblastic nephroma and leiomyosarcoma should be differentiated.     

A sheep survived for 48 days with the biventricular bypass type total artificial heart

A biventricular bypass type total artificial heart (BVB-TAH) utilizing two pusher-plate pumps was developed and implanted in a sheep for 48 days with excellent results. A Hall effect sensor was utilized to operate each pump independently with a full stroke at variable rates (VR). With this system, the animal's hemodynamics was kept physiologically, and all metabolic parameters except hemoglobin and hematocrit returned to normal three weeks after implantation. However, signs of infection appeared on the forty-second day, and consequently the animal fell into a state of shock. Even at that time the BVB-TAH maintained circulation by increasing pumping rate automatically. On the forty-eighth day, the animal could not stand and suffered from anuria; the experiment was then terminated after 1,140 h pumping. At autopsy, there was an enlarged heart with an atrophic change, 1,900 ml of pleural effusion, and 3,100ml of ascites fluid. Blood culture taken on the forty-seventh day yielded Acinetobacter calcoaceticus. The BVB-TAH operated in an independent VR mode maintained entire circulation, and has a capability of substituting the native heart function in any situation.     

Synergistic effect of 1,25-dihydroxyvitamin D3 and retinoic acid in inducing U937 cell differentiation.

We examined the effects of retinoic acid (RA), 1,25-dihydroxyvitamin D3 (1,25-(OH)2D3), and its synthetic analogue, 22-oxa-1,25-(OH)2D3, on differentiation of U937 cells by studying the cellular growth, surface marker expression and cytosolic free Ca2+ concentration ([Ca2+]i). RA inhibited cellular growth but did not induce expression of Mo2 (CD14), a monocyte/macrophage specific surface marker. To the contrary, 1,25-(OH)2D3 did not inhibit cellular growth, but increased CD 14-positive cells. Simultaneous addition of 1,25-(OH)2D3 and RA had no additive effect on cellular growth inhibition or CD14 expression. With regard to [Ca2+]i, however, 5 days' incubation with either of them increased the basal [Ca2+]i level and induced U937 cells to respond to formyl-methionyl-leucyl-phenylalanine (FMLP). When the cells were incubated with both 10(-6) M RA and 10(-8) M 1,25-(OH)2D3, basal [Ca2+]i was higher and FMLP caused a greater increase in [Ca2+]i than when only RA or 1,25-(OH)2D3 was added. These data suggest that RA and 1,25-(OH)2D3 induce monocytoid differentiation in U937 cells through different pathways and act synergistically in the differentiation process. The 22-oxa-1,25-(OH)2D3 induced CD14 expression, basal [Ca2+]i increase and [Ca2+]i response to FMLP, but did not cause cellular growth inhibition in U937 cells, and in these points, 22-oxa-1,25-(OH)2D3 exhibited no significantly different effects from 1,25-(OH)2D3. Thus, 22-oxa-1,25-(OH)2D3 has the same potent activity as 1,25-(OH)2D3 in inducing differentiation of U937 cells.     

Myocardial protective effect of lidocaine during experimental off-pump coronary artery bypass grafting.

Off-pump coronary artery bypass grafting (OPCABG) has recently gained popularity. During OPCABG, patients remain vulnerable to ischemic-reperfusion injury due to a temporary coronary occlusion without any active cardioprotection. Some strategies such as ischemic preconditioning (IP) and an intracoronary shunt have been applied with a view to minimizing the effects of ischemia, but the effects of these strategies remain controversial. This study was carried out to investigate the protective effect of lidocaine against myocardial ischemic-reperfusion injury. Twenty-one pigs were assigned to three groups, each consisting of seven pigs. In the control group, using a left internal thoracic artery (LITA) bypass circuit, the left anterior descending coronary artery (LAD) was occluded for 45 min followed by two hours of reperfusion. In the IP group, five min of occlusion followed by 15 min of reperfusion was performed. In the lidocaine group, 2 mg/kg of lidocaine was administered directly into the LAD just before the LAD occlusion. Infarct size expressed as a percentage of the area at risk was significantly smaller in the lidocaine group (2.7+/-4.2%) than in the control group (79.9+/-6.0%, p<0.001) or the IP group (57.0+/-25.9%, p<0.001). Lidocaine exhibited a potent myocardial protective effect in the present OPCABG model.     

Neurotized nevi of the oral mucosa: an immunohistochemical and ultrastructural analysis of nevic corpuscles

BACKGROUND: Nevic corpuscle (NC), a stacked lamellar structure reminiscent of Meissner corpuscle, is frequently observed in dermal melanocytic nevi. Although the heading 'neurotized' is classically used for these nevi, the exact neural nature of NC has been a topic of considerable debate. Neurotized nevi have received little attention in the dental literature, and there was no information on NC in oral melanocytic nevi. METHODS: Six cases of oral intramucosal nevi with a significant number of NC (two completely and four partially neurotized nevi) were examined immunohistochemically and ultrastructurally. RESULTS: NC was composed of closely piled laminar cells devoid of visible melanin. NC and associated spindle nevus cells were immunopositive for S-100 protein but negative for HMB-45, myelin basic protein and epithelial membrane antigen. Within NC, no reactivity for neurofilament protein, protein gene product 9.5 or peripherin was evident. Numerous CD34-positive dendritic cells were located between nevus cells and often encircled NC. Ultrastructurally, NC consisted of concentrically layered elongated cells with a slender lamellated cytoplasm rich in thin filaments and pinocytotic vesicles. Their cytoplasmic processes were focally covered by external basal lamina and continuous to spindle nevus cells. Occasional NC cells contained a few melanosomes. There was no interposed axon in NC. CONCLUSIONS: Despite the close resemblance to Meissner corpuscle, NC showed no axonal supply. NC cells lacked terminal Schwannian differentiation and appeared to be modified melanocytes with some perineurial ultrastructural characteristics. The presence of CD34-positive cells, presumably corresponding to endoneurial fibroblasts, further supports an organizational relationship of NC and peripheral nerve sheath elements.     

Overestimation of myocardial viability due to an increase in thallium uptake by the lung

Thallium lung uptake (TL-uptake) was usually treated as background for myocardial image and increase of TL-uptake in exercise test was considered as marker of depressed cardiac function. It was reported that marked increase of TL-uptake in patients with acute myocardial infarction (AMI) corresponded to acute severe congestive heart failure. Here effect of TL-uptake on myocardial planar images was studied in 61 patients with AMI. In acute phase anterior, LAO 30 degrees and LAO 60 degrees myocardial images were collected. In 29 cases of 61 cases 3 to 6 hours delayed images could be collected. Each myocardial images was divided to 3 division and both images were compared. In 5 of 6 patients with marked increase of TL-uptake new defects were noted in anterior division of delayed images and in one case also in lateral division. In 7 patients of 12 patients with moderate increase of TL-uptake new defects were also noted in delayed images, i.e. 3 in anterior, 3 in inferior and one in apical division. It was concluded that over estimation of myocardial viability due to marked increase of TL-uptake was often noted in patients with AMI accompanying severe congestion. It became clear that delayed images were necessary to correctly estimate myocardial viability in such case.