Cadherin-6 mediates the heterotypic interactions between the hemopoietic osteoclast cell lineage and stromal cells in a murine model of osteoclast differentiation

Osteoclasts are multinucleated cells of hemopoietic origin that are responsible for bone resorption during physiological bone remodeling and in a variety of bone diseases. Osteoclast development requires direct heterotypic cell-cell interactions of the hemopoietic osteoclast precursors with the neighboring osteoblast/stromal cells. However, the molecular mechanisms underlying these heterotypic interactions are poorly understood. We isolated cadherin-6 isoform, denoted cadherin-6/2 from a cDNA library of human osteoclast-like cells. The isolated cadherin-6/2 is 3,423 bp in size consisting of an open reading frame of 2,115 bp, which encodes 705 amino acids. This isoform lacks 85 amino acids between positions 333 and 418 and contains 9 different amino acids in the extracellular domain compared with the previously described cadherin-6. The human osteoclast-like cells also expressed another isoform denoted cadherin-6/1 together with the cadherin-6. Introduction of cadherin-6/2 into L-cells that showed no cell-cell contact caused evident morphological changes accompanied with tight cell-cell association, indicating the cadherin-6/2 we isolated here is functional. Moreover, expression of dominant-negative or antisense cadherin-6/2 construct in bone marrow-derived mouse stromal ST2 cells, which express only cadherin-6/2, markedly impaired their ability to support osteoclast formation in a mouse coculture model of osteoclastogenesis. Our results suggest that cadherin-6 may be a contributory molecule to the heterotypic interactions between the hemopoietic osteoclast cell lineage and osteoblast/bone marrow stromal cells required for the osteoclast differentiation. Since both osteoclasts and osteoblasts/bone marrow stromal cells are the primary cells controlling physiological bone remodeling, expression of cadherin-6 isoforms in these two cell types of different origin suggests a critical role of these molecules in the relationship of osteoclast precursors and cells of osteoblastic lineage within the bone microenvironment.     

A comparative analysis of the rheographic indices of the pancreatic blood flow in patients who have undergone a subtotal gastric resection and gastrectomy

Overall ninety-two patients with carcinoma of the stomach were studied, 45 of whom had undergone subtotal resection, and 47--gastrectomy. During the first postoperative 10 days a study was made of the pancreatic hemocirculation by contact bipolar rheography. After surgery on the stomach, the pancreas shows phasic changes in bloodflow that include the time of arterial hyperemia, that of insufficiency of arterial blood-filling, and time period of restoration of bloodflow. Fluctuations in pancreatic arterial blood filling in those patients who had survived gastrectomy within the first 48 hours following the operation are more definite than in those having undergone subtotal resection of the stomach.     

The Veterans Affairs Implantable Insulin Pump Study: effect on cardiovascular risk factors

OBJECTIVE: To determine whether implantable insulin pump (IIP) and multiple-dose insulin (MDI) therapy have different effects on cardiovascular risk factors in insulin-requiring patients with type 2 diabetes. RESEARCH DESIGN AND METHODS: A randomized clinical trial was conducted at seven Veterans Affairs medical centers in 121 male patients with type 2 diabetes between the ages of 40 and 69 years receiving at least one injection of insulin per day and with HbA1c, levels of > or =8% at baseline. Weights, blood pressures, insulin use, and glucose monitoring data were obtained at each visit. Lipid levels were obtained at 0, 4, 8, and 12 months, and free and total insulin levels were obtained at 0, 6, and 12 months. All medications being taken were recorded at each visit. RESULTS: No difference in absolute blood pressure, neither systolic nor diastolic, was seen between patients receiving MDI or IIP therapy, but significantly more MDI patients required anti-hypertensive medications. When blood pressure was modeled against weight and time, IIP therapy was significantly better than MDI therapy for systolic blood pressure in patients with BMI <33 and for diastolic blood pressure in patients with BMI >34 kg/m2. Total cholesterol levels decreased in the overall sample, but IIP patients exhibited significantly higher levels than MDI patients. Triglyceride levels increased over time for both groups, with IIP patients having significantly higher levels than patients in the MDI group. BMI was a significant predictor of, and inversely proportional to, HDL cholesterol level. No difference in lipid-lowering drug therapy was seen between the two groups. Free insulin and insulin antibodies tended to decrease in the IIP group as compared with the MDI group. C-peptide levels decreased in both groups. CONCLUSIONS: IIP therapy in insulin-requiring patients with type 2 diabetes has advantages over MDI therapy in decreasing the requirement for antihypertensive therapy and for decreasing total and free insulin and insulin antibodies. Both therapies reduce total cholesterol and C-peptide levels.     

Preparation of the myristoylated and nonmyristoylated form of recombinant recoverin in E. coli cells and comparison of their functional activity]

Numerous data strongly suggest the involvement of cytokines and the matrix metalloproteinase collagenase (MMP-1) in the pathogenesis of periodontitis. Recently, we have demonstrated that, upon culturing under the influence of IL-1 alpha + EGF, a large amount of inactive procollagenase (MMP-1) is stored in the extracellular matrix of periosteal tissue. We now show that this endogenous reservoir of proenzyme can be operative after activation with plasmin and is able to induce a rapid and almost complete breakdown of the collagenous extracellular matrix. The level of collagen degradation following activation showed a strong correlation with the amount of proenzyme that was incorporated in the tissue. The highest level of degradation (70% of the total amount of collagenous proteins) was found with the IL-1 alpha + EGF-treated explants, followed by those treated with IL-1 alpha alone (35%). Explants cultured with EGF or in the absence of cytokines, containing only small amounts of procollagenase, showed little collagen breakdown following plasmin activation (7%). Inhibition of metalloproteinases by EDTA, or blockage of plasmin by PMSF, prevented the degradation in all explants irrespective of the amount of proenzyme present in the tissue. Our findings demonstrate that endogenous proenzyme stored in a native connective tissue matrix can be activated at a later time interval which results in a massive breakdown of the tissue. This study shows a possible pathway of collagenase-induced breakdown without recent de novo synthesis of the enzyme. Such a sequence may be operative in chronic inflammatory diseases, such as periodontitis, where production of procollagenase under the influence of cytokines spans a longer time period, whereas breakdown is often characterized by a cyclic behaviour.     

Performance monitoring of the EC - 1030 system by a microprocessor - based monitor

This paper presents a M6800 microprocessor based hardware monitor for measuring certain selected parameters of the EC-1030 computer system. The motivation for this work was to get an insight into the operation of the system under the present work load and use these results towards improvement and design studies. The three main classes of quantitative indices of computer system performance/productivity, responsiveness and use have been measured using hardware and software tools. This paper describes the hardware monitor design and discusses the measurements made.     

Calculation of the interaction of supersonic counter flows

The maximum stable difference scheme of second order accuracy is described for axisymmetrical flows with shock waves and the results are given of a calculation of the interaction between an external supersonic flow and a counter supersonic jet issuing from a cylindrical channel.Translated from Inzhenerno-Fizicheskii Zhurnal, Vol.27, No.3, pp. 430–437, September, 1974.     

Magnito-, electro- and echocardiography in detecting symptoms of the "hypertensive heart"

The study compared diagnostic potential of magnetocardiography (MCG), electrocardiography (ECG) and echocardiography (echo-CG) in 18 patients with arterial hypertension (AH). 32 healthy males served as control. Elements of MCG from normal subjects have been analyzed morphologically in 36 points of precordial leads. Left ventricular hypertrophy was registered at echo-CG, MCG, ECG in 11 (61%), 16 (84%) and 7 (34%) of the AH patients, respectively. Left atrial hypertrophy was discovered primarily by echo-CG and MCG. Defects in ventricular repolarization were recorded by MCg in 7 (39%) patients basing on MCG, echo-CG and rarely ECG signs of left ventricular hypertrophy. MCG is recommended as an effective tool in diagnosis of "hypertensive heart".     

Isolation of a novel Helicobacter species, Helicobacter cholecystus sp. nov., from the gallbladders of Syrian hamsters with cholangiofibrosis and centrilobular pancreatitis

A filamentous, gram-negative, motile bacterium with a single polar sheathed flagellum was isolated from gallbladders of hamsters with cholangiofibrosis and centrilobular pancreatitis. Bacteria grew under microaerophilic conditions at 37 and 42 degrees C, were oxidase, catalase, arginine aminopeptidase, and L-arginine arylamidase positive, reduced nitrate to nitrite, were resistant to cephalothin, and exhibited intermediate susceptibility to nalidixic acid. Sequence analysis of the 16S rRNA gene indicated that the bacterium was a novel member of the Helicobacter genus, most closely related to Helicobacter pametensis. We propose to name this bacterium Helicobacter cholecystus. In epidemiologic studies, isolation of H. cholecystus correlated strongly with the presence of cholangiofibrosis and centrilobular pancreatitis; however, further studies are needed to define the role of this bacterium in pathogenesis.