Stimulation of gelatinase B and tissue inhibitors of metalloproteinase (TIMP) production in co-culture of human osteosarcoma cells and human fibroblasts: Gelatinase-B production was stimulated via up-regulation of fibroblast growth factor (FGF) receptor

Co-cultures of human osteosarcoma Takase (OST) cells with various human fibroblasts derived from surgical specimens stimulated production of gelatinase B (92-kDa type-IV collagenase, MMP-9), tissue inhibitors of metalloproteinase (TIMP)-1, and TIMP-2 when compared to cultures of individual cells. The maximum stimulation of gelatinase-B production occurred at a cellular ratio of I:I. Conditioned media from several fibroblast cultures stimulated OST cells to produce gelatinase B, TIMP-1 and TIMP-2, but not vice versa. Among various recombinant growth factors or cytokines, tumor necrosis factor (TNF)-α stimulated gelatinase-B production in cultures of OST cells alone, while recombinant basic fibroblast growth factor (bFGF) stimulated gelatinase-B production in co-cultures of OST cells with skin fibroblasts but not in individual cultures of each cell type. In the co-cultures, gelatinase-B production was inhibited by anti-bFGF monoclonal antibody (MAb), but not by anti-TNF-αMAb. This co-culture-specific stimulation of gelatinase-B production by bFGF was associated with increased expression of the FGF receptor in the co-culture. © 1996 Wiley-Liss, Inc.     

Hypersensitivity of NIH3T3 cells transformed by H-RAS gene to DNA-topoisomerase-I inhibitors

We examined the effects of the introduction of H-ras oncogene into murine cell line NIH3T3 on growth inhibition by topoisomerase-I (topo-I) inhibitors. The H-ras-transformed cells (pT22-3) showed approximately 12-fold increased sensitivity to a novel topo-I inhibitor, NB-506 [6-N-formylamino-12, 13-dihydro-I, II-dihydroxy-13-(β-D -glucopyranosyl)-5H-indolo(2,3-a)pyrrolo(3,4-c) carbazole-5,7(6H)-dione], compared with the parental NIH3T3 cells. pT22-3 also showed increased sensitivity to other topo-I inhibitors such as camptothecin (approx. 3.0-fold) and CPT-II (irinotecan, approx. 3.0-fold). Transformation of NIH3T3 by another oncogene (erb82) did not affect their sensitivity to these topo-I inhibitors. pT22-3 had approximately 32-fold higher topo-I activity than NIH3T3, but the same topo-I content. In a cell-free system, topo-I activity was increased 2-fold by addition of the H-ras protein precipitated from pT22-3 cells. Topo I in the nuclear extract of pT22-3 was eluted easily by low concentrations of NaCl compared with that of NIH3T3, suggesting a qualitative change in pT22-3 topo I. Increased phosphorylation of topo I was observed in pT22-3. Furthermore, NB-506 decreased the amount of the GTP-bound form of the H-ras product in pT22-3 cells. These results suggest that the high growth-inhibitory effect of a topo-I inhibitor, NB-506, on H-ras-transformed NIH3T3 cells is due to the H-ras-mediated signal-transduction pathway. © 1996 Wiley-Liss, Inc.     

Anti-DNA antibody kinetics following selective removal by adsorption using dextran sulphate cellulose columns in patients with systemic lupus erythematosus

The aim of this study is to determine by mathematical analysis which of two models, the one- or the two-compartment model, more closely approximates the kinetics of anti-dsDNA following immunoadsorption procedures in patients with systemic lupus erythematosus. Titers of anti-dsDNA were measured at specified intervals after apheresis to each model by nonlinear least-squares methods, and Akaike's Information Criterion (AIC) was calculated to determine which model most approximately described the kinetics. The A1C of the two-compartment model was larger than that of the one-compartment model in all 14 SLE patients (P < .001). Therefore, the one-compartment model is thought to be suitable. The generation rate and catabolic rate of anti-dsDNA were obtainable using this model. The anti-dsDNA replenishment curve after an immunoadsorption session was defined by only two parameters: the generation and catabolic rates of anti-dsDNA. © 1996 Wiley-Liss, Inc.     

Chemotaxis of human articular chondrocytes and mesenchymal stem cells

Migration of chondrocytes and mesenchymal stem cells (MSCs) may be important in cartilage development, tissue response to injury, and in tissue engineering. This study analyzed growth factors and cytokines for their ability to induce migration of human articular chondrocytes and bone marrow‐derived mesenchymal stem cells in Boyden chamber assays.In human articular chondrocytes serum induced dose‐ and time‐dependent increases in cell migration. Among a series of growth factors and cytokines tested only PDGF induced a significant increase in cell migration. The PDGF isoforms AB and BB were more potent than AA. There was an aging‐related decline in the ability of chondrocytes to migrate in response to serum and PDGF. Human bone marrow MSC showed significant chemotaxis responses to several factors, including FBS, PDGF, VEGF, IGF‐1, IL‐8, BMP‐4, and BMP‐7. In summary, these results demonstrate that directed cell migration is inducible in human articular chondrocytes and MSC. PDGF is the most potent factor analyzed, and may be useful to promote tissue integration during cartilage repair or tissue engineering. © 2008 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 26:1407–1412, 2008     

Sutureless patch repair for small blowout rupture of the left ventricle after myocardial infarction

Rupture of the left ventricular free wall is one of the most serious complications of myocardial infarction. A 73-year-old man with severe chest pain visited our hospital. Coronary angiography revealed acute myocardial infarction in the territory of the diagonal branch. About six hours after successful percutaneous coronary intervention, the patient fell into cardiogenic shock with chest pain. Echocardiography showed moderate pericardial effusion with a subepicardial hematoma, and percardioentesis led to the diagnosis of free wall rupture. Emergency surgery was performed with the use of intra-aortic balloon pumping. The rupture was a blowout type in a small tear at the anterolateral wall of the left ventricle. We repaired the tear with an off-pump sutureless patch using collagen fleece with fibrinogen-based impregnation (TachoComb™) and equinous pericardium with fibrin spray. The patient was free of both re-rupture and pseudoaneurysm postoperatively, and was discharged 20 days after the operation. Considering previously reported various procedures for surgical repair, this technique may be useful if the tear is small.     

Analysis of the Combined Effect of 1-Menthol and Ethanol as Skin Permeation Enhancers Based on a Two-Layer Skin Model

The combined effects of 1-menthol and ethanol as a skin permeation enhancer were evaluated with two equations describing the permeability coefficient through full-thickness skin (P _FT) and the full-thickness skin/vehicle concentration ratio (C _FT/C _V) of drugs as a function of their octanol/vehicle partition coefficient (K _OV). A two-layer model was applied for skin, which consists of a stratum corneum (SC) with lipid and porous pathways and a viable epidermis and dermis (ED). The two equations contain one variable (K _OV) and nine coefficients, six of which (three diffusion coefficients, the porosity of the SC, and two terms of the linear free energy relationship) were considered different, dependent on the drug vehicle. In vitro permeation of four drugs (morphine hydrochloride, atenolol, nifedipine, and vinpocetine) was determined using excised hairless rat skin and four aqueous vehicles (water, 5% 1-menthol, 40% ethanol, and 5% l-menthol–40% ethanol) to measure each P _FT. Drug concentrations in full-thickness skin were also measured to obtain C _FT/C _V. A nonlinear least-squares method was employed to determine six coefficients using the two equations and experimentally obtained P _FT and C _FT/C _V. The addition of 1-menthol to water and 40% ethanol increased the diffusion coefficient of drugs in lipid and pore pathways of SC, whereas the addition of ethanol to water and 5% 1-menthol increased the drug solubility in the vehicle, decreased the skin polarity, and increased the contribution of the pore pathway to whole-skin permeation.     

So-called "immature dentinoma": a case presentation and histological comparison with ameloblastic fibrodentinoma

The existence of the "dentinoma" as an independent entity has not been fully accepted, recently being regarded as an ameloblastic fibroma with formation of dentin and named an ameloblastic fibrodentinoma. However, there are histological differences between the several cases reported previously as "immature dentinoma" and the ameloblastic fibrodentinoma. This paper presents a case report of a dentin-forming intraosseous benign tumor without any histological features of ameloblastic fibroma. The patient was a 30-year-old woman with a rather well-circumscribed intraosseous lesion of the mandibular left premolar area. Histologically. the lesion consisted of dentin–like tissue with a tubular structure and globular calcifications, numerous epithelial strands and islands without enamel organ-like structure, and a cellular fibrous component without a primitive dental papilla-like appearance. The present case and a review of the literature suggest that epithelial elements in odontogenic fibroma-like lesions may occasionally have an inductive effect for dentin or dentin-like tissue formation.     

Cellular kinetics and lectin distribution in hamster buccal carcinomas

As part of an evaluation of the progression to malignancy, the cellular kinetics of DMBA-induced tumors in the buccal mucosa of hamsters were examined using 5-bromodeoxyuridinc (BrdU), peanut agglutinin (PNA), Ulex curopaeus agglutinin I (UEA-I) and wheat germ agglutinin (WGA). BrdU-positive cells were localized in the basal layer in both normal and hyperplastic epithelium, whereas they were distributed from the basal to the prickle cell layer in squamous cell carcinoma (SCC). The extent of BrdU labeling increased as the tissues progressed towards malignancy. PNA and UEA-I showed binding only in the prickle cell layer of normal and hyperplastic epithelium, and WGA showed binding mainly in the prickle cell layer. However, in SCC. PNA and UEA-I showed no binding in the prickle cell layer and WGA binding was observed throughout the epithelium. A study of cellular kinetics using BrdU labeling and the lectin binding pattern may be useful in the evaluation of tissue changes on the way to malignancy.     

Asphyxiating thoracic dystrophy: Surgical correction and 2-year follow-up in a girl

Summary A 15-month-old girl under mechanical ventilation with asphyxiating thoracic dystrophy underwent surgical thoracic expansion according to the procedure of Toddet al. (1986). Now age 4 years, she is free from respiratory distress, is of normal intelligence, and leads an active life.