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Objective: To evaluate the effects of various 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors (statins) on ectopic osteoinduction by recombinant human bone morphogenetic protein-2 (rhBMP-2) using different administration methods. Materials and methods: Disks containing 5 μg of rhBMP-2 and type I collagen were implanted into the calf muscles of 6-week-old male rats (n = 64). Either the lactone form of simvastatin (SV), open hydroxy-acid form of simvastatin (SVA), cerivastatin (CVA), or vehicle (control) was then administered per orally (PO group) or subcutaneously (SC group) for 20 days. The disks were removed on day 21 after implantation, and ectopic induced bone formation was evaluated by radiographic, histologic, and biochemical analysis. Results: Both the projected and radiopaque area on X-ray film, and the calcium content of the SV group in the SC group (SV–SC group) were significantly greater than those in the other SC and PO groups. Alkaline phosphatase activity and tartrate-resistant acid phosphatase activity in the SV–SC group were significantly lower than those in the other SC and PO groups. Histologic examination revealed an increase of ectopic induced bone volume in the SV–SC group. Conclusion: Subcutaneous administration of SV stimulates ectopic osteoinduction by rhBMP-2 through reduction of bone turnover.

Phosphodiesterase (PDE) 3 has been characterized in isolated rat submandibular acini. PDE3 activity was detected in homogenates of isolated rat submandibular acini; little or no PDE3 activity was found in ducts. About 62% of PDE3 activity in the acini was recovered in the supernatant fractions; 38% in particulate fractions. In the acini, but not ducts, PDE3A mRNA was detected by reverse transcriptase-polymerase chain reaction (RT-PCR). The PDE3-specific inhibitor, cilostamide, increased the ratio of apomucin mRNA/18s rRNA, as quantified by real-time RT-PCR. Our results indicate that PDE3A may be important in regulating cAMP pools that control acini functions.

Objective: To investigate the characteristics of ectopic chondroid/bone matrix and chondrogenic/osteogenic cells induced by recombinant human bone morphogenetic protein-2 (rhBMP-2). Materials and methods: rhBMP-2 (5 μg) combined with atelocollagen was implanted into calf muscles of rats and removed on days 7, 10, 14, 21, or 28. Tissue sections were examined using: (i) hematoxylin/Alcian blue/Sirius red stain, (ii) enzyme histochemistry for alkaline phosphatase (ALP) and tartrate-resistant acid phosphatase activity, (iii) immunohistochemistry for types I, II, and X collagen, and (iv) electron microscopy. Results: On day 7, numerous fibroblast-like cells with ALP activity were present on the pellet rim. On day 10, chondroid matrix (CM) had formed, contained both type I collagen and proteoglycans, and often continued into the BMP pellet. On day 14, bone-like matrix formed around hypertrophic chondrocytes simultaneously with endochondral ossification. Coexpression of types I and II collagen within chondrocytes and osteocytes was observed throughout the time course of the experiment. Conclusion: These results suggest that fibroblast-like cells invading the pellet differentiate into chondrocytes and form CM under the scaffold of the carrier component. It appears that some chondrocytes change their phenotype to produce the bone-like matrix and remain within the endochondral bone. This process enables rapid osteogenesis to occur.

Reverse transcription-polymerase chain reaction (RT-PCR) analysis revealed that HOSM-1 cells, an osteosarcoma cell line established from human mandible, expressed mRNA for osteoblastic markers, such as alkaline phosphatase, osteonectin, osteocalcin and parathyroid hormone receptor, thus exhibiting an osteoblastic phenotype. We have investigated a possible role of cyclic nucleotide phosphodiesterases (PDEs) in osteosarcoma cells. RT-PCR analysis revealed that HOSM-1 cells expressed mRNA for PDE4A, 4B and 4C. In addition, rolipram, a specific inhibitor of PDE4, inhibited HOSM-1 cell proliferation. The finding that PDE4 is involved in proliferation of osteosarcoma cells suggests the possibility that PDE4 may be a new target for antitumor therapy.

Dermatomyositis (DM) is a diffuse inflammatory disease accompanied by weakness in the proximal muscles of the limbs that belongs to the collagen family of diseases whose onset is induced by autoimmune disorders. DM is characterized by the presence of cutaneous symptoms, such as erythema keratodes on the dorsal surface of the phalangeal joints (Gottron’s sign) and edematous erythema of the eyelids (Heliotrope erythema).1 Although the disease is often complicated by the development of malignant tumors,2 it is extremely rare that such patients develop malignant tumors in the oral region. This report describes the case of a 19-year-old male with DM who later developed tongue cancer and reviews the literature dealing with DM over the last 10 years.

When subjective uncertainties are taken into account in structural reliability analysis and subjective evaluations are given in terms of fuzzy sets, we encounter the problem of how to combine a number of evaluations. In this paper, several combination methods used in the field of structural reliability engineering were first examined with respect to the following two points: (i) if the result of combination is independent of order of combination, and (ii) if the result of combination is reasonable when a variety of evaluations are combined. No method examined was found to satisfy both of the conditions. Then, a new combination method was proposed. The method was obtained by modifying Nishimura et al's combination method which was based on Dempster's rule and the concept of vagueness. Modifications were made in treatment of empty sets and vagueness. The method gives the same result independent of the order of combination, and also gives a reasonable result when a variety of evaluations are combined. Furthermore, by using the combination method proposed and preparing five membership functions and three vagueness functions for choice, a way was given for taking account of subjective uncertainties in structural reliability analysis.

The activity, expression and function of phosphodiesterase 4 (PDE 4) were investigated in the HMG human gingiva-derived malignant melanoma cell line. A specific PDE4 inhibitor, rolipram, inhibited PDE activity in homogenates of HMG cells, and PDE4B and 4D mRNAs were detected by RT-PCR in RNA from HMG cells. Two specific PDE4 inhibitors, rolipram and Ro-20-1724, and an adenylate cyclase activator, forskolin, increased intracellular cAMP in HMG cells. Cell growth induced by rolipram, Ro-20-1724, and forskolin was inhibited by the H-89 protein kinase A (PKA) inhibitor. However, in contrast to effects of H-89, two other PKA inhibitors, KT5720 and PKI, did not inhibit rolipram-induced cell growth. A cAMP analogue that selectively activates Epac, 8-pCPT-2'-O-Me-cAMP, also promoted the growth of HMG cells. These findings suggested that PDE4, PDE4B and/or 4D regulate cell growth through cAMP targets in the HMG malignant melanoma cell line. There have been no previous studies of positive regulation of cell growth by PDE4 inhibition, suggesting that it may be possible to target PDE4 in therapy for human malignant melanoma.

Purpose: In this study we evaluated pedunculated oncocytic carcinoma (OC) in the buccal mucosa via immunohistochemical and ultrastructural studies. Patient and methods: An 84-year-old man was referred to our clinic with a pedunculated mass about 4 cm in diameter in the right buccal mucosa. An incision biopsy revealed the diagnosis of oncocytic tumor, and enucleation was performed. The tumor was stained for immunohistochemical analysis using the ABC method and antibodies against cytokeratin (CK), epithelial membrane antigen (EMA), desmin, S-100 protein and muscle-specific actin, respectively. The tumor was stained with uranyl acetate and lead citrate for visualization by electron microscopy. Results: Histopathology results revealed that the tumor consisted of oncocytic cells, characterized by eosinophilic and granular cytoplasm, and atypical nuclei. These cells had infiltrated local blood vessels, salivary glands and muscles. Immunohistochemical staining indicated that these cells were positive for CK and EMA, and negative for desmin, muscle-specific actin and S-100 protein. Electron microscopy revealed numerous dilated cytoplasmic mitochondria, and the cell contours and nucleic shapes of tumor cells were often irregular. Conclusions: Because the histopathologic features of OC are similar to those of benign oncocytoma, the diagnosis of OC must be confirmed by a combination of clinical and ultrastructural characteristics.

Immunolocalization of endogenous bone morphogenetic protein-2 (BMP-2) was investigated during the process of ectopic bone formation induced by recombinant human BMP-2 (rhBMP-2). Pellets consisting of 5 μg of rhBMP-2 and 6 mg of atelopeptide type I collagen (AC) were implanted into the calf muscles of 6-week-old rats. On days 7, 10, 14, 21 and 28 after implantation, tissue specimens were removed and examined immunohistochemically by light and electron microscopy after incubation with anti-BMP-2 monoclonal antibodies. Immunolocalization by light microscopy showed BMP-2 in chondrocytes at the pellet rim on days 7 and 10, in osteocyte-like cells in the chondroid matrix on day 14, and in osteocytes in the newly formed bone on days 21 and 28 after implantation. Ultrastructurally, on days 7 and 10 after implantation, immunolabelling for BMP-2 was aggregated in vesicle-like matrices released from mature chondrocytes in the chondroid matrix. On day 14, immunolabelling against BMP-2 had accumulated in vesicle-like matrices embedded in the calcified cartilage, in the cytoplasmic vacuoles of chondroclasts absorbing the matrix, and at the resorption surface of the calcified cartilage. On days 21 and 28, BMP-2 immunolabelling was seen in the osteoid layer and osteocyte lacunae. These results suggest that the chondrocytes and osteocytes induced by rhBMP-2 produce endogenous BMP-2. It seems that part of the endogenous BMP-2 that accumulated in the chondroid matrix was absorbed by chondroclasts and then participated in the osteoblastic differentiation of immature mesenchymal cells. This study indicates that, in addition to the implanted exogenous rhBMP-2, endogenous BMP-2 plays an important part in the maintenance of the bone-formation cascade during ectopic osteoinduction.

The participation of endogenous BMP-2 in the process of ectopic osteoinduction by rhBMP-2 implanted into rat muscles was investigated using immunohistochemistry, immunoelectron microscopy, in situ hybridization and real-time RT-PCR. Our results suggested that not only implanted exogenous rhBMP-2 but also endogenous BMP-2 produced by osteogenic and/or chondrogenic cells participates in the rapid progression of ectopic bone formation cascade. Since the statins promote the expression of endogenous BMP-2 and enhance the bone formation, we next examined the stimulative effect of statins on the rhBMP-2-induced osteogenesis, by radiological and biochemical analysis, and histology. These results indicated that subcutaneously injected simvastatin promotes rhBMP-2-induced ectopic bone formation by reducing bone turnover. Simvastatin may become a useful adjuvant therapy for enhancing BMP-2 induced bone formation.

右中幹気管支上部発生のmucoepiderrnoid tumorに対し中下葉切除を行った1治験例を報告する. 初回生検診断は扁平上皮癌であり, 術前に放射線治療も行われたが効果は無かった. 切除標本は組織学的には充実性増殖部分が多く, 異型度の強い細胞が見られ, 分化度は低いと考えられたが, 進行度は肺門型早期肺癌に相当した. 文献的に見て, この様な管内限局型は予後が良く, 転移も見られない. 本症例も予後良好と予想されるが, 術後5ヶ月健在である.

The rate constant for the bimolecular reaction CO + N 2 O → CO 2 + N 2 was determined by comparison of calculated infrared emission profiles of CO 2 with those observed in shock-tube experiments in the temperature range 1350–2100 K for CO-N 2 O-He-Ar mixtures. The rate constant was found to be k 1 = 3.2 × 10 11 exp(−85 kJ/ RT ) cm 3 mol −1 s −1 .

Summary Among the applications of diagnostic radiology in malignant lymphoma, G.I. examination and lymphography have been discussed. It is extremely important to accurately evaluate the extent of the lesion by use of radioisotopes as well as other X-ray studies. Since the disease is characterised by a high radiosensitivity, adequate radiation therapy should result in some healing and a prolongation of life even in advanced cases. Diagnosis and treatment are quite intimately related in this disease.