Activation of phospholipase D by platelet-derived growth factor (PDGF) in rat C6 glioma cells: possible role in mitogenic signal transduction.

The effects of platelet-derived growth factor (PDGF) on phospholipase D (PLD) activity and deoxyribonucleic acid (DNA) synthesis in rat C6 glioma cells have been investigated. Pretreatment of serum-starved C6 cells with PDGF results in enhanced choline production and the phosphatidylethanol (PEt) formation in the presence of ethanol, indicating the activation of PLD acting on phosphatidylcholine (PC). The dose-response curve for choline generation and DNA synthesis were comparable. In addition, the effects of PDGF on both PEt formation and [3H]thymidine incorporation into acid-precipitable material was blocked by the potent protein kinase C (PKC) inhibitor 1-(5-isoquinolinesulphonyl)-2-methylpiperazine (H-7) but not by N-(2-guanidinoethyl)-5-isoquinolinesulphonamide (HA1004), a relatively weak inhibitor of PKC, suggesting that PDGF plays an important role as a positive regulator of glioma cell growth via a PLD-mediated mitogenic signal transduction cascades, which depends largely on the activation of PKC.     

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.     

Synthesis, pharmacological activity and biopharmaceutical characteristics of alpha,2-dimethyl-5H-[1]benzopyrano[2,3-b]pyridine-7-acetates

The pro-drugs of alpha,2-dimethyl-5H-[1]benzopyrano[2,3-b]pyridine-7-acetic acid(I) with a potent anti-inflammatory activity were synthesized in order to reduce its gastrointestinal side effects. Various esters synthesized were evaluated for their anti-inflammatory activity and ulcerogenicity. Among the compounds maintaining a potent activity of I, N,N-dimethylcarbamoylmethyl alpha,2-dimethyl-5H-[1]benzopyrano[2,3-b]pyridine-7-acetate (II-18) showed excellent biopharmaceutical characteristics. The ulcerogenic effect of II-18 on the rat gastric mucosa was about 3 times less than that of I. It was suggested that II-18 may be an useful biolabile pro-drug for I among the compounds tested.     

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.     

Axonal dystrophy in the posterior column nuclei of young adult epileptics with chronic phenytoin intoxication

Axonal spheroids in the posterior column nuclei of phenytoin-intoxicated epileptics were classified according to their predominant subcellular components into six types, and their incidences were compared with those in controls. Spheroids from phenytoin-intoxicated epileptics showed significantly higher proportions of the tubulomembranous (TM) and layered membrane loop (LML) types in the gracile nucleus, appearance of the same types in the cuneate nucleus, and a significant decrease of the neurofilamentous (NF) type in both nuclei. The incidences of the complex body (CB) and granular material types and of the homogeneous dense-body (HDB) type, which appeared only in the gracile nucleus, showed no difference between the intoxicated patients and the controls. The NF, CB and HDB types were therefore considered to be nonspecific. It was thought that chronic phenytoin intoxication might induce dystrophic changes, such as those characterized by the presence of the TM and LML types, in the axon terminals of the gracile and cuneate nuclei, possibly due to some abnormalities of the axoplasmic transport system.     

Immunohistochemical study of fibronectin, lysozyme, and alpha-fetoprotein (AFP) in human hepatocellular carcinoma

We have immunohistochemically localized fibronectin, lysozyme and alpha-fetoprotein (AFP) in 21 human hepatocellular carcinoma (HCC) tissues obtained by surgical resection at both light and electron microscopic levels. Three distinct distribution patterns of fibronectin (sinusoidal, periacinar, and pericellular patterns) were observed. The sinusoidal and periacinar patterns were mainly observed in HCC of pseudoglandular or trabecular patterns and of Edmondson's grade I or II, whereas the pericellular pattern was observed in HCC of compact or trabecular patterns and of Edmondson's III grade, suggesting that the pericellular fibronectin was rather associated with undifferentiated HCC. Electron microscopic observation of the pericellular fibronectin showed fibronectin to be present in the dilated intercellular spaces where microvilli were moderately developed. We observed intracytoplasmic staining of fibronectin in 2 of the 21 HCC cases. By immunoelectron microscopy, fibronectin was observed in the endoplasmic reticulum (ER) of some HCC cells. In the 21 HCC cases, lysozyme-positive cancer cells were observed in 10 cases, and AFP in 6 cases. At the ultrastructural level, lysozyme was identified in the ER and the perinuclear spaces of HCC cells, suggesting that lysozyme was synthesized by these cells. Lysozyme-positive cases tended to be more frequently observed in cases with the pericellular pattern of fibronectin rather than those with sinusoidal or periacinar patterns.