Possible involvement of arachidonic acid metabolism in phenobarbital promotion of hepatocarcinogenesis

The effects of inhibitors of arachidonic acid metabolism andantioxidants on the rat liver tumor promotion activity of phenobarbital(PB) were assessed using the enzyme-altered focus as the end-pointlesion. Fischer 344 male rats were initiated with N-nitrosodiethylamine(200 mg/kg) and then divided into five groups placed on basaldiet, diet containing 0.05% PB, diet containing 0.05% PB plus0.75%, 1% or 1.5% levels of various inhibitors of arachidonicacid metabolism or antioxidants, or diet containing 1% or 1.5%inhibitors or antioxidants alone for 10 weeks, and then killed.-Bromo phenacyl bromide, an inhibitor of phospholipase A₂ significantly inhibited the promotion activity of PB at dose levelsof 0.75% and 1.5%, reaching plateau at 0.75%. Both quercetin,an inhibitor of lipoxygenase, and morin, a dual inhibitor oflipoxygenase-cyclooxygenase, significantly reduced the promotionactivity of PB at the 1.5% but not 0.75% dose levels. Moreover,acetylsalicylic acid, an inhibitor of cyclooxygenase dose-dependentlyinhibited the promotion activity of PB. Among the antioxidantsinvestigated, vitamin E did not affect, but n-propyl gallateand ethoxyquin exerted a dose-dependent inhibition of PB promotion.These results are strongly suggestive of an involvement of phospholipaseA₂ lipoxygenase and cyclooxygenase arachidonic acid metabolicpathways in the mechanisms underlying PB enhancement of hepatocarcinogenesis.     

Mechanical power during maximal treadmill walking and running in young and elderly men

This study determined mechanical power during movements specific to maximal walking and running using a non-motorized treadmill in 38 elderly [69.4 (5.0) years] and 50 young [24.3 (3.4) years] men. The mean mechanical power over a period of time covering six steps, during which the belt velocity peaked and then kept almost plateau, was determined as a performance score in each of maximal walking (WP) and running (RP). In terms of the value relative to body mass, the relative difference between the two age groups was greater for RP (61.7%) than for WP (21.4%) or isometric knee extension (34.1%) and flexion torque (43.8%). In the two groups, WP was significantly (P<0.05) correlated to knee extension (r=0.582 for the elderly and r=0.392 for the young) and flexion torque (r=0.524 for the elderly and r=0.574 for the young). Similarly, RP was also significantly (P<0.05) correlated to knee extension (r=0.627 for the elderly and r=0.478 for the young) and flexion torque (r=0.500 for the elderly and r=0.281 for the young). In these relationships, the WP adjusted statistically by thigh muscle torque was similar in the two age groups. However, the corresponding value for RP was significantly higher in the young than in the elderly. The findings here indicate that: (1) the difference between the young and elderly men in mechanical power is greater during maximal running than maximal walking, and (2) although the thigh muscle torque contributes to the power production during the two maximal exercise modes in the two age groups, the RP is greater in the young than in the elderly regardless of the difference in the thigh muscle torque.     

Diazepam reduces both arterial blood pressure and muscle sympathetic nerve activity in human

It is known that benzodiazepines have a hypotensive effect, but the mechanism has not been well elucidated yet. To clarify whether this effect is due to central or peripheral mechanism, we administered 5 mg of diazepam or saline intravenously to healthy volunteers and assessed the change in blood pressure, heart rate, muscle sympathetic nerve activity and heart rate variability. After diazepam administration, systolic and mean blood pressure decreased significantly. Muscle sympathetic nerve activity was also significantly reduced but heart rate did not change, whereas the variables of spectral analysis of heart rate variability did not show significant change. We concluded that the hypotensive effect of diazepam in human is mainly due to the central mechanism.     

SOLITARY PLASMACYTOMA OF THE SUBMANDIBULAR LYMPH NODE WITH STROMAL AMYLOID DEPOSITS

This report concerns a case of solitary extramedullary plasmacytoma of the left submandibular lymph node in a 56-year-old man. The tumor showed monoclonal proliferation of abnormal plasma cells which revealed highly positive stainings of both methylgreen pyronin and kappa light chain using the immunoperoxidase technique in the cytoplasms, and further revealed massive'.amyloid'deposits in the stroma, which suggested the possibility of sequential amyloid formation upon the secretion of paraprotein by tumor cells.     

Histological examination of beta-tricalcium phosphate graft in human femur

Prominent osteoconductive activity and the biodegradable nature of beta tricalcium phosphate (beta-TCP) for bone grafts in animal experiments has been reported. A new type of beta-TCP has been manufactured at extraordinarily high purity and has been available as potent bone grafting substitute for clinical use. The histological features of grafted beta-TCP in human bone have been analyzed. A 33-year-old female with a bone tumor of the proximal femur underwent curettage and beta-TCP graft under the diagnosis of probable benign fibrous dysplasia. Four weeks later, the proximal femur, including the grafted beta-TCP was resected because of the final diagnosis of the curettaged materials was osteosarcoma. The resected specimen revealed abundant direct new bone apposition on beta-TCP. There was no cartilaginous tissue or enchondral ossification. Bone formation was more prominent in the periphery of the grafted area than in the center. There was a considerable number of osteoclast-like giant cells surrounding the beta-TCP. This case illustrated that highly purified beta-TCP had prominent osteoconductive activity and biodegradable nature in human bone.     

TUMOR CELL PHAGOCYTOSIS AND CYTOTOXICITY OF LYMPHOBLASTOID CELLS FOLLOWING CONCANAVALIN A TREATMENT

Cell-to-cell interaction was investigated in various malignant tumor cells (human ovarial tumor, lung cancer, carcinoma of larynx and hamster melanoma cell) and in human lymphoblastoid cells (T-cell (MOLT-4 cell), thymoma cells and B-cells (Burkitt lymphoma cell)). Live lymphoblastoid cells did not adhere to the cell surfaces of tumor cells nor the lymphoblastoid cells were ingested by tumor cells wihout immunologic and specific treatment. Tumor cells as well as T-cells and B-cells had receptors to concanavalin A on their surfaces, and they showed marked cell binding of tumor cells and lymphoblastoid cells. Moreover, tumor cells that phagocytized lymphoblasts underwent marked cell destruction within 4 hours of cell binding. The cytolytic mechanism of the target tumor cell was probably related to contact with the lymphoblastoid cells and was increased by ingestive activity, and metabolic disturbance by lymphotoxin in tumor cells.     

Vascular endothelial growth factor overproduced by tumour cells acts predominantly as a potent angiogenic factor contributing to malignant progression

To elucidate the role of vascular endothelial growth factor (VEGF), an endothelial cell-specific mitogen, in tumour angiogenesis and malignant progression, an expression vector harboring human VEGF cDNA was stably transfected into three human cancer cell lines with poor VEGF productivity. Though their in vitro growth rate and intrinsic productivity of another angiogenic factor, basic fibroblast growth factor (bFGF), were not changed by transfection, those clones with higher VEGF production were endowed with tumorigenic and angiogenic potentials as follows: firstly, nontumorigenic, lung carcinoma QG90 cells having lower bFGF productivity acquired tumorigenicity as well as significant in vivo angiogenesis-inducing ability, secondly, tumorigenic colorectal carcinoma RPMI4788 cells having higher potency for bFGF production could form more vascularized solid tumour with faster growth rate and thirdly, oestrogen-dependent breast carcinoma MCF-7 cells, which did not produce detectable bFGF, acquired tumorigenicity even in the absence of oestrogen and the solid tumour growth rate was remarkably enhanced, accompanied with increased vascularization, in the presence of oestrogen. These results suggest that tumour progression closely depends on angiogenesis, and VEGF significantly contributes to malignant progression of a variety of tumour cells through its potent angiogenic activity, independent on the bFGF productivity of tumour cells.     

7 Fälle von Plasmozytome

In diesen Jahhren haben wir einez unehmende Zahl des Beispielsfalls von Pasmozytome auch bei uns in Japan. Und obwohl es noch eine Frage bleibt, ob wir diese Tatsache als wirkliche Zunahme der Krankheit annehmen können, wollen wir hier ihre 7 Fälle berichten, die wir neulich beobachten. Wir bemerken an ihrer klinischen Diagnose zuerst den Schmerz und Anämie, die der Destruktion des Knochensubstanzes entspringen, geringe Leukozytose und die Beschleunigung der Blutsenkungsgeschwindigkeit, es sind aber vor allem der Elektrophorese-Diagram des Serums und die Erscheinung der Paraprotein im Harn, die mit der Krankheit am engsten zusammenhängen. Trotzdem müssen wir darauf achten, daß diese zwei bezeichenden Befunde seltenerweise ausbleiben können (Tbb. 1, 2).