Cell death of osteocytes occurs in rat alveolar bone during experimental tooth movement.

The purpose of this study was to examine the morphological changes in alveolar bone osteocytes on the pressure side during experimental tooth movement, using quantitative evaluation on hematoxylin and eosin-stained sections, the TUNEL method, confocal laser scanning microscopy (CLSM), and transmission electron microscopy. In 8-week-old Wistar rats, the left first molar was forced to move mesially with an average load of 10 g by a nickel-titanium superelastic wire. After 6 hours, nuclear condensation and fragmentation appeared in osteocytes adjacent to the hyalinized periodontal ligament (PDL). These cells showed TUNEL-positive reaction. The number of osteocytes with apoptosis progressively increased up to 1 day. At 1 and 2 days, cytoplasmic and nuclear destruction and distribution within the lacunae occurred and increased up to 4 days. The proportion of necrotic osteocytes and near empty lacunae peaked at 2 and 4 days, respectively. At 7 days, necrotic osteocyte and empty lacunae numbers returned to the level of control bone, probably due to resorption of the alveolar bone containing apoptotic and necrotic osteocytes. Ultrastructually, the osteocytes showed apoptotic morphology at 6 and 12 hours and 1 day; at 2 and 4 days, several osteocytes exhibited characteristics of necrosis and destructive images of the surrounding bone matrix, which resulted in enlargement of the lacunae. The present results demonstrate that osteocytes in alveolar bone adjacent to the hyalinized PDL underwent cell death via apoptosis and "secondary necrosis" during orthodontic tooth movement, which may be associated with the subsequent bone resorption.

Wavelength specific activation of PI 3-kinase by UVB irradiation.

We investigated the effect of UVB irradiation on phospholipid metabolism using normal human diploid skin fibroblasts. When cells were exposed to monochromatic UV light, the intracellular PIP3 level was increased within 1 min in a wavelength-specific manner. The increase was most marked in the UVB range and was inhibited by a PI 3-kinase inhibitor, tyrosine kinase inhibitor, or antioxidant reagents. Furthermore, the decrease of cell viability induced by UVB irradiation was significantly blocked by wortmannin. These results suggest that PI 3-kinase activation is involved in novel cellular responses specific for UVB that lead to cell death.

[A case of primary mucinous adenocarcinoma of jejunum].

A 73-year old woman consulted our hospital for consciousness disorder and was hospitalized under a diagnosis of cerebral infarction. On admission, retention of a large volume of ascites was noted. There were also marked increases in tumor markers. Serum CEA, CA19-9 and CA125 levels were 871.9 ng/ml, 1048.2U/ml, and 444.7U/ml, respectively. Cytological examination of the ascites showed class V. Abdominal CT showed a mass measuring 4 cm in diameter and dilatation of the small intestinal tract. During detailed examination, she developed ileus. Fluoroscopy through the lung tube suggested a small intestinal tumor. Laparotomy was performed to relieve ileus. In the abdominal cavity, the greater omentum formed a mass due to dissemination. Tumor was found in the jejunum approximately 60 cm from Treitz's ligament toward the anal side. Omentectomy and partial jejunectomy were performed. Macroscopic findings showed tumor protruding from the mucosal surface. Histological diagnosis was mucinous adenocarcinoma. Primary small intestinal cancer is very rare. In particular, only one case of mucinous adenocarcinoma of the small intestine was reported in Japan. We reported the second case in Japan with a review of the literature.

Synergistic induction of metallothionein synthesis by interleukin-6, dexamethasone and zinc in the rat.

We investigated the reciprocal effects of interleukin-6 (IL-6), glucocorticoid and zinc (Zn) on metallothionein (MT) synthesis in rats. MT synthesis in the liver, which is a key responsible organ in acute phase responses, was induced by IL-6 or dexamethasone (Dex), and in an additive manner by a combination of IL-6 and Dex 18 h after injection. MT synthesis in the lung and heart was evaluated by immunoassay using a specific antibody to MT-1, because of its low concentration in these tissues. Heart concentrations of MT-1 were significantly increased by IL-6, and were further increased by the combination of IL-6 and Dex, although Dex by itself had no effect. This suggests a synergistic effect of IL-6 and Dex on MT-I synthesis in the heart. A similar synergism was observed in the lung. To study the effect of Zn on the induction of MT and acute phase proteins, Zn, IL-6 and Dex were administered in various concentrations. The increase in liver MT induced by the combination of IL-6 and Dex with Zn (130 micrograms MT/g of liver) was greater than the sum of the increases induced by (IL-6 + Zn) and by (Dex + Zn) (103 micrograms MT/g), suggesting a synergistic increase. The data indicate that the maximal increase in the induction of MT by a combination of IL-6 and Dex depends on an adequate liver Zn content. Thus, the in vivo synergistic induction of acute phase proteins by IL-6, glucocorticoid and Zn may be required for the maximal and rapid response, not only in liver but also in other tissues including heart and lung. This suggests that the synergistic reaction may be important for an enhancement of the radical scavenging ability of tissues in acute phase responses.

Susceptibility of metallothionein-null mice to paraquat.

Using transgenic mice in which metallothionein (MT)-I and MT-II genes, we have studied a putative role of MT as a free radical scavenger against paraquat, a free radical generator. Male mice were injected s.c. with paraquat (PQ) at a single dose of 40 or 60 mg/kg of body weight (b.w.). Two of the six MT-null mice died within 16 h at the dose of 60 mg PQ/kg. b. w. PQ administration increased hepatic MT concentration in the normal mice (C57BL/6J), but not in the MT-null mice. The lipid peroxidation (LP) determined by thiobarbituric acid-reactive substance formation was increased by PQ in the liver of normal and MT-null mice, and the enhanced level was greater in the MT-null mice than in the C57BL/6J mice. Administration of PQ significantly increased blood urea nitrogen only in the MT-null mice, indicating renal damage. Without paraquat administration, the hepatic concentration of non-protein sulphydryl compounds was less in the MT-null mice than in the C57BL/6J mice, and the basal level of LP was higher in the MT-null mice than in the C57BL/6J mice. The present results support the notion that MT plays an antioxidative role against paraquat insult under physiological conditions.

Characteristics of tissue plasminogen activator from paranasal mucous membrane in chronic sinusitis.

Tissue extract of paranasal mucous membrane from patients with chronic sinusitis was found to show a large lysis area on plasminogen-rich fibrin plates, but not on plasminogen-free fibrin plates. This indicates the existence of tissue plasminogen activator in the tissue extract. Further studies by the gel filtration technique showed that two plasminogen activators of different molecular weights were present in the tissue extract. The existence of tissue plasminogen activator with a low molecular weight has not previously been reported. This activator is labile at neutral pH at 37 degrees C, but stable on fibrin under the above conditions. The molecular weight of this compound is lower than that of cytochrome c. It may be a compound which is proteolytically modified by proteases, ie, trypsin-like enzymes, existing in the paranasal mucous membrane tissue of patients with chronic sinusitis.

Differences in physicochemical properties between tissue plasminogen activators from human paranasal mucous membrane and pig heart.

In order to clarify the physicochemical property of tissue plasminogen activator (TA), tissue extracts of human paranasal mucous membrane and pig heart were studied by the biochemical techniques. The studies by gel filtration revealed that two plasminogen activators of different molecular weight were present in the extract of human paranasal mucous membrane. The existence of tissue plasminogen activator with a low molecular weight (LMW-TA) has not previously been reported. This molecular weight of this compound was lower than that of cytochrome c. On the other hand, the molecular weight of tissue plasminogen activator from pig heart (PH-TA) was similar to that of ovalbumin, about 46,000 daltons, as estimated by Sephadex G-150 gel filtration. From the physicochemical property of LMW-TA, it is suggested that the LMW-TA from paranasal mucous membrane with chronic sinusitis was produced by proteases, i.e. trypsin-like enzyme, present in the mucous membrane with chronic inflammation.

Fibrinolytic activity in patients with acute tonsillitis.

Three parameters in blood fibrinolysis, viz, the levels of fibrinogen, plasminogen, and fibrinogen and/or fibrin degradation products (FDP), were measured in patients with acute tonsillitis and the results were compared with those for healthy adults. The fibrinogen content in acute tonsillitis increased significantly (P less than .001), that of plasminogen decreased significantly (P less than .005), while FDP showed a higher value (P less than .01). The significance of the fibrinolytic system in acute tonsillitis is discussed.