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Biomedical subjects

S Wysocki

Publications and source records attributed to S Wysocki.

At least 37 records · Page 2Linked to original sources

Recombinant human bone morphogenetic protein-2 enhances expression of interleukin-6 and transforming growth factor-beta 1 genes in normal human osteoblast-like cells.

The process of recombinant human bone morphogenetic protein-2 (rhBMP-2)-induced endochondral ossification involves 1) the proliferation and differentiation of mesenchymal cells into chondroblasts and osteoblasts; 2) the production and maturation of cartilage and bone matrix; and 3) the differentiation of circulating osteoclast precursor cells into osteoclasts. Currently the molecular mechanisms of these complex sequential events are unknown. It seemed reasonable to us to assume that communication between cells through soluble mediators during bone induction by rhBMP-2 may play an important role in the sequential differentiation of chondroblasts, osteoblasts, and osteoclasts. We have therefore used a human osteoblast-like initial transfectant cell line (HOBIT) to study the effect of rhBMP-2 on gene expression of interleukin-6 (IL-6) and transforming growth factor-beta 1 (TGF-beta 1), both of which affect osteogenesis and ostoeclastogenesis. Our results have demonstrated that rhBMP-2 acts on HOBIT cells to stimulate expression of IL-6 and TGF-beta 1 genes and the production of IL-6. Enhancement of gene expression of IL-6 and TGF-beta 1 by rhBMP-2 was both sensitive (half maximal effect at approximately 10 ng/ml) and potent (maximum induction was approximately four and threefold greater than controls, respectively). Time course studies showed that the induction of TGF-beta 1 and IL-6 mRNA occurs within short periods--4 and 8 hours after exposure to rhBMP-2, respectively. Interestingly, these effects, however, were not accompanied by the mitogenic action of rhBMP-2. It suggests that rhBMP-2 enhances IL-6 and TGF-beta 1 production during osteogenesis and at least in part mediates the complex sequential differentiation of chondroblasts, osteoblasts, and osteoclasts during rhBMP-2-induced endochondral ossification.

Blotting, Northern↗

Carbonic anhydrase II gene transcript in cultured osteoclasts from neonatal rats: effect of calcitonin.

Carbonic anhydrase II (CA II), an enzyme catalyzing the interconversion of CO2 and water to HCO3- and protons, has a key role in osteoclastic bone resorption, but little is known of the regulation of CA II gene expression by calcitonin. Analysis of mRNA in osteoclasts has been difficult because of the problems of obtaining sufficient number of purified osteoclasts from bone. In this study, however, we have investigated the regulation of CA II mRNA in rat osteoclasts and their putative mononuclear precursors by using in situ hybridization. We have found that the CA II gene is expressed at high levels in osteoclasts and what are probably their maturing mononuclear precursors. Measurement of CA II mRNA in cultured osteoclasts and their putative mononuclear precursor cells by cytophotometry provided evidence that calcitonin, a direct inhibitor of mammalian osteoclast activity, reduces the levels of CA II mRNA in a dose dependent manner; maximum reduction was observed at a concentration of 100 pM of calcitonin. In addition, calcitonin reduced the number of CA II mRNA-positive mononuclear precursor cells. The results also suggest that expression of the CA II gene is a feature of cells committed to the osteoclast lineage.

Acid Phosphatase↗

Detection of mRNA for carbonic anhydrase II in human osteoclast-like cells by in situ hybridization.

Carbonic anhydrase II (CA II) plays an important role during osteoclastic bone resorption. Biochemical investigations of gene expression of CA II, however, have been hampered by difficulty in obtaining sufficient numbers of purified osteoclasts. In this study, we describe a nonradioactive, digoxigenin-labeled cDNA in situ hybridization technique capable of determining the pattern of CA II gene expression in human osteoclast-like cells (OC-like cells) at the single-cell level. The results showed that CA II mRNA was located in the cytoplasm of both imprinted and cultured OC-like cells from a giant cell tumor of bone. On the other hand, no evidence of CA II mRNA was found in either the mononuclear cells (tumor cells) of giant cell tumor of bone or osteosarcoma cells. There is a significant correlation between in situ hybridization and northern blot analysis for CA II mRNA in both the giant cell tumor of bone and the osteosarcoma. Our results also indicated that quantitation of in situ hybridization can be achieved by computed cytophotometry.

Adult↗

Expression of histone and alkaline phosphatase genes in UMR 106-01 rat osteoblast-like cells exposed to the Hoechst dye H33342.

The fluorescent Dye H33342 (H342) is a bis-benzimidazole used for intravital fluorescent staining. In this report, we found that H342 completely abolished histone 2a mRNA but had no effect on alkaline phosphatase gene expression and protein synthesis in UMR 106-01 rat osteoblast-like cells. The complete loss of histone 2a mRNA occurred after only 20 min of treatment with H342. This effect is unlikely to be a result of inhibition of DNA synthesis, which was only partly suppressed. The mechanism of the action of H342 on histone 2a mRNA is presently unknown.

Alkaline Phosphatase↗

The reliability of highly elevated CA 19-9 levels.

CA 19-9 is used as a tumour marker of the upper gastrointestinal tract. However, extremely elevated CA 19-9 levels are found also in patients with benign diseases. Cholestasis was present in 97.1% of patients with high elevated CA 19-9, independent of their primary disease. 50% of patients with non-malignant diseases and increased CA 19-9 levels showed liver cirrhosis, cholecystitis, pancreatitis and/or hepatitis. In 8.8% no explanation was found for the extremely high CA 19-9 level. The results provide evidence of different factors influencing the CA 19-9 level.

Antigens, Tumor-Associated, Carbohydrate↗

[Inflammatory intestinal tumor as a cause of thrombocytopenia].

The acquired thrombocytopenia is part of a large number of diseases caused by a variety of different factors. Besides the classical failure of bone marrow proliferation respectively the replacement of the bone marrow with malignant cells, there are immunological disorders and many substances which may cause thrombocytopenia. The diagnosis of an "idiopathic thrombocytopenia" is sometimes posed even at the end of intensive diagnostic efforts. Possibly a benign neoplasia is also to cause a massive decrease of thrombocytes. We observed preoperatively in one patient with extensive stenosis of the sigma, caused by an inflammatory tumor a thrombocytopenia with a level under 50,000/ml. A normalization in thrombocyte blood counts appeared spontaneously after tumor resection.

Aged↗

Innovations in contraception: the Norplant system.

The Norplant (Huhtamaki Oy/Leiras Pharmaceuticals, Turku, Finland) contraceptive system is a safe, highly effective, reversible method of hormonal contraception. The system consists of six flexible match-size implants that are implanted in the inner aspect of the upper arm. This sustained-release system delivers the progestin levonorgestrel at levels sufficient to prevent pregnancy for as long as 5 years. Norplant is a convenient, easy-to-use method. Adequate counseling of potential users and appropriate selection of patient users are important determinants of patient satisfaction with Norplant.

Adult↗

Common infections in the history of cancer patients and controls.

The association between the frequency of manifest infectious diseases and cancer risk was investigated in a case-control study at Heidelberg, FRG. A total of 255 cases with carcinomas of the stomach, colon, rectum, breast, and ovary, as well as 255 population controls and 230 hospital controls were interviewed using a standard questionnaire. Controls were matched to the cases for age, sex, and region of residence at the time of the interview. A history of common colds or gastroenteric influenza prior to the interview was found to be associated with a decreased cancer risk. Thus the odds ratios for "three or more common colds per year (on average)" versus "no common cold within the last 5 years prior to the interview" were 0.18 (95% CI = 0.05-0.69) and 0.23 (95% CI = 0.06-0.89) relative to population controls and hospital controls, respectively. There was no apparent relationship between childhood infections or other diseases reported in the earlier history, and cancer risk. While the findings are supported by previous studies and fit well into the results of other fields of cancer research, a conclusive interpretation and biological explanation cannot yet be given.

Adult↗

[Composition of gallbladder and bile duct calculi].

The composition of gallbladder and bile duct stones removed at the time of cholecystectomy was analysed in a consecutive series of 45 patients. The type of stones at the two sites was similar in all but two patients. Cholesterol content differed by more than 20% in only six patients. Cholesterol stones were found in the gallbladder of 33 patients, in the bile duct of 36 patients (73 and 80%, respectively); mixed stones in eight and five patients, respectively (18 and 11%); brown-pigment stones in three patients each (7%); black-pigment stones in one patient each (2%). Bile duct stones overlooked during cholecystectomy are thus suitable for litholysis, e.g. by irrigation with monooctanoin, in the majority of cases.

Bile Duct Diseases↗