[Chest pain: analysis of a cardiological consultation].
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Biomedical subjects
Publications and source records attributed to A Bloch.
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ML-1 human myeloblastic leukemia cells, suspended in RPMI-1640 medium, differentiated to monocyte or macrophage-like cells when either tumor necrosis factor-alpha (TNF-alpha), transforming growth factor-beta (TGF-beta), or tetradecanoylphorbol acetate (TPA) was added prior to or simultaneously with fetal bovine serum (FBS). When FBS was applied first, and followed, after washing, by the cytokines or by TPA, maturation did not occur. A 77 kDa glycoprotein (DF77), isolated from human leukocyte-conditioned medium and present in FBS, was capable of replacing FBS for induction of differentiation. Thus, in this cell system, TNF-alpha, TGF-beta, and TPA acted as competence factors, whereas DF77 acted as the progression signal. Optimal competence was established after exposure of the cells to TPA or to either of the cytokines for approximately 2 or 30 min, respectively. After removal of the factors, competence was retained for approximately 3 hr before it declined. These results demonstrate that the initiation of ML-1 human myeloblastic leukemia cell differentiation relied upon the sequential and ordered input of competence and progression signals.
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ML-1 human myeloblastic leukemia cells are induced to differentiate to monocytes by conditioned medium (CM) derived from tetradecanoylphorbol acetate (TPA)-treated ML-1 cells. Antibodies to tumor necrosis factor (TNF) inhibited the differentiation-stimulating activity of CM, indicating that this activity is due to the presence of TNF in CM. TNF added to non-conditioned medium was as effective as CM in stimulating ML-1 cell differentiation. In the presence of a low (0.12 ng/ml) concentration of TPA, TNF-induced maturation was synergistically increased and Type I macrophages were formed. With higher (1-10 ng/ml) TPA concentrations, Type II macrophages were also obtained. As the TNF/TPA concentration increased, ML-1 cell differentiation was increasingly inhibited. Mature cells derived from ML-1 cells were found to secrete TNF at concentrations ranging from less than 2 U/ml to greater than 180 U/ml, the amount depending upon the number of cells and the stage of cell maturation. These results indicate that TNF participates in the regulation of precursor cell maturation. Low concentrations of TNF produced by small numbers of mature cells stimulate differentiation, whereas high concentrations of TNF generated by elevated numbers of macrophages inhibit the maturation process, possibly in combination with other cytokines. Because TNF serves as a competence factor for ML-1 cells, (Guan X.-P., Takuma T., Hromchak R. & Bloch A. (1990) Competence and progression in cell differentiation. Proc. Am. Assoc. Cancer Res. 31, 28.), the TNF-induced stimulation of differentiation depends additionally on the action of serum-contained differentiation-specific progression factors.
Colorectal cancer is the third most common malignant neoplasm worldwide. Epidemiological and laboratory animal studies have established a link between various nutritional factors and the etiology of this cancer. Recent studies in genetic epidemiology and molecular biology have shown that inherited genetic factors also play an important role in colorectal carcinogenesis. Thus, genetic-nutritional interactions may form the basis for the development of this cancer. Nutritional factors that appear to promote or attenuate the carcinogenic process in the colon include fat, excess calories, fibre, calcium, selenium, and various vitamins. Strategies for primary prevention of colorectal cancer should therefore be targeted to all populations who are at risk because of dietary and hereditary predisposition. Based on current knowledge, recommended nutrition guidelines for reducing the risk of colon cancer include decreased fat consumption, adequate amounts of fruits, vegetables, and calcium, and avoidance of overweight. Research to further elucidate the role of diet in colorectal carcinogenesis should include randomized studies in humans, testing of various nutritional regimens, and the use of colonic adenomas and markers of cell proliferation and differentiation as end-points.
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In recent years there has been increasing concern and involvement of Israeli adolescents with dieting. An increase in the incidence of obesity has been emphasized by the mass media. This has been marked by an increase in the number of questions on dieting sent anonymously by 12 to 14 year-olds to a column in a popular youth magazine about adolescent sexuality. These letters include requests for diets to prevent obesity in general and fatness of certain parts of the body in particular, such as the thighs or buttocks; questions as to side-effects of diets already started, particularly amenorrhea; and questions about the onset of bulimia and anorexia nervosa, expressing fear of the consequences. This study gives examples of the questions and the answers, and indicates the professions of those to whom the applicants were referred for further diagnosis and treatment. Newer techniques of health education with regard to adolescent dieting are urgently needed so that the health staff can promote insight and indicate the need for treatment at as early a stage as possible. The use of mass media in a suitable manner is critical, given the increase in diet-advertising.
Colour Doppler is a recent and important development among non-invasive diagnostic techniques in cardiology. A series of 500 adults has been studied in order to define the contribution made by colour Doppler to conventional Doppler. After elimination of patients with normal echo Doppler studies, colour Doppler contribution has been considered useful in 51% of the cases and was essential in 13%. Main contributions have been noted in valvular regurgitations, multiple valvular lesions, prosthetic valves and congenital cardiopathies. Colour Doppler appears as an useful, but not as an indispensable complement to conventional Doppler in adult cardiology.
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The aim of this study involving 700 echocardiographic examinations (echoes) was to evaluate the diagnostic impact of the method for right heart abnormalities. Among 200 two-dimensional echoes of a first series we found 23 abnormalities (11.5%): nine congenital malformations, seven pulmonary hypertensions, four cases of isolated right ventricular dilatation, two tricuspid regurgitations (TR), one right atrial myxoma. In four cases the abnormality was clinically unexpected. In a second series of 500 patients, consecutively subjected to a two-dimensional echo with pulsed-wave and continuous-wave Doppler, we found 119 regurgitations of right heart valves in 98 patients (20%): 35 TR and 24 pulmonary regurgitations (PR) secondary to pulmonary hypertension, 13 TR secondary to tricuspid valve prolapse, 16 TR and 11 PR as a part of polyvalvular disease; 10 TR and 10 PR were isolated observations. The examination technique and the echo signs of the principal abnormalities of the right heart are reviewed. In summary, we emphasize that right heart abnormalities are surprisingly frequent in routine echo investigations; therefore, complete study of all the right heart structures in every echo examination is mandatory.
The development and the maintenance of a tissue involves the sequential differentiation of precursor cells along multiple intermediate stages of maturity. At these stages the cells can proliferate or differentiate depending upon the growth or differentiation signals they receive. Terminally mature cells lose their ability to proliferate. Alterations can occur at the level of the cell or the whole organism that lead to the sustained proliferation of incompletely mature cells. This process constitutes an oncogenic event, and the cellular and molecular changes that lead to its occurrence are surveyed in this review.
Enteral feeding is often required in patients with cancer of the head and neck. Percutaneous endoscopic gastrostomies (PEGs) and jejunostomies (PEJs) can facilitate enteral feeding in patients who require this treatment. The endoscopic technique allows for the placement of feeding gastrostomies and jejunostomies without a surgical procedure and eliminates the need for nasal tubes for long-term enteral feeding. Forty-two patients with head and neck tumors were referred for placement of PEGs because of severe dysphagia induced by tumors, surgery, radiation, or chemotherapy. The procedure was performed in the gastroenterology suite. Patients were sedated with intravenous meperidine and diazepam, and local anesthetic with lidocaine was applied to the area of incision. Average procedure time was approximately 20 minutes. The procedure was successful in 39 patients in whom tubes were placed ranging in diameter from 15F to 22F. PEGs were placed in 36 patients with intact stomachs and PEJs in three patients with previous gastrectomies. The remaining three procedures were unsuccessful because of technical reasons. There were three localized skin infections, and all responded to antibiotic therapy. Neither peritonitis nor any other immediate complication occurred. In 16 nonhospitalized patients, the procedure was performed on an outpatient basis. After a mean followup of 4.5 +/- 6 months of enteral feeding in the home, there was only one case of aspiration and subsequent pneumonia, and this case responded to antibiotics. No other long-term complications were noted. Thus feeding gastrostomies and jejunostomies can be placed safely and easily in patients with cancers of the head and neck by endoscopic methods without abdominal surgery. These tubes can be used for enteral feeding and eliminate the need for nasogastric tubes. They are better tolerated, are of a wider diameter, and have a reduced risk for migration, clogging, and aspiration-related complications.
Tumor necrosis factor-alpha and transforming growth factor-beta, like 12-O-tetradecanoylphorbol 13-acetate, induce differentiation of ML-1 human myeloblastic leukemia cells along the monocyte path. As measured at 5 min following exposure of the cells to either of these agents, extensive translocation of protein kinase C from the cytosolic to the membrane fraction occurred. A correlation was observed to exist between protein kinase C translocation, cell differentiation, and cessation of cell growth induced by transforming growth factor-beta and tumor necrosis factor-alpha.
Human recombinant tumor necrosis factor (rTNF) bound to ML-1 and HL-60 human myeloid leukemia cells in a bimodal manner. Saturable high-affinity binding was maximal at approximately 3 nmol/L rTNF, whereas saturable low-affinity binding reached its maximum at approximately 30 nmol/L. As analyzed by computer program, the observed data fit a two-receptor site model, with p less than .05. High-affinity binding concentrations of rTNF caused the differentiation of both cell lines, whereas low-affinity binding concentrations abolished this effect in a concentration-dependent manner. Thus, the type of biologic response elicited with rTNF in these cells is a function of the concentration at which the factor is applied. If generally applicable, this bimodal effect may require consideration when rTNF is to be used therapeutically.
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The capacity for continuous proliferation (immortalization) of ML-1 human myeloblastic leukemia cells derives from their sensitivity to growth factors and their insensitivity to differentiation factors (DF) at the limiting concentrations at which these are present in the culture medium. Upon increasing the concentration of DF, or after treatment with DNA-specific anticancer agents, the cells exit the proliferation program and differentiate to monocyte/macrophage-like cells (Y. Honma, C. Honma, and A. Bloch, Cancer Res., 46: 6311-6315, 1986). The study reported here shows that when ML-1 cells, induced to differentiate with DF contained in mitogen-stimulated human leukocyte-conditioned medium (CM) are treated with the carcinogen N-nitroso-N-methylurea, their differentiation program is interrupted and proliferation is resumed at a stably increased rate of growth (doubling time, 25.1 versus 31.3 h). This "step-up" transformation is brought about by only a narrow concentration range of carcinogen, acting at a restricted time interval following differentiation induction. The step-up transformed cells are more sensitive to growth factor signals and less sensitive to DF signals than are untreated ML-1 cells. When retreated with a higher concentration of DF and the same concentration of N-nitroso-N-methylurea, the transformed cells undergo a further decrease in doubling time to 21 h. Differentiation-uninduced ML-1 cells do not respond to treatment with N-nitroso-N-methylurea, indicating that differentiation-induced cells, at an early stage of the maturation process, may be the targets for the carcinogen-mediated transformation.