Health promotion, health protection, and preventive services

Health promotion, health protection, and preventive services reflect the 21 priority areas of Healthy People 2000. This article focuses on the cost-effectiveness of health promotion and the role that primary care physicians can play in this initiative.     

Concurrence of Graves'' disease and dysplastic cerebral blood vessels of the moyamoya variety

A recent observation that (+)-7-deaza-5'-noraristeromycin (1), as an L-like analogue of aristeromycin, possessed meaningful anti-trypanosomal properties has prompted a search of other 7-deazapurines with similar or improved anti-trypanosomal responses. In that direction a series of pyrazolo[3,4-d]pyrimidines (that is, 8-aza-7-deaza-5'-noraristeromycin derivatives, 2-11) related to 1 have been prepared. These derivatives were evaluated against bloodstream forms of Trypanosoma brucei brucei and Trypanosoma brucei rhodesiense grown in vitro. Of these compounds, the parent L-like derivative 2 was less potent (IC50 40-70 microM) than 1 (IC50 0.165-5.3 microM) whereas the D-like analogue 3 was inactive, which is the same trend observed previously with 7-deaza-5'-noraristeromycin. Interestingly, some moderate activity (IC50 12.2-16.8 microM) was seen in the D-like 4'-methyl derivative 7 while its L-like partner was inactive.     

Individual perceptions of stress by dentists

This paper is concerned with individual responses of four dental practitioners to stress. The subjects were chosen on the basis of age, sex, length of time in practice and whether or not they practised solo or in a group. Responses were measured against ten stressor variables that were previously found to have occurred commonly among dentists. From these responses stressor ratings of the four subjects were obtained and compared. These ratings, which seem to be idiosyncratic and unpredictable, reflect wide differences between the respondents. The findings suggest the possibility that these differences may be attributable to personality factors and differences in coping styles, and tend to support the hypothesis that stress is a unique, perceptual and experimental phenomenon.     

Cardiac morphology and left ventricular function in normotensive morbidly obese patients with and without congestive heart failure, and effect of weight loss

BACKGROUND: Prevention of hypothermia during abdominal surgery by insulating or heat-transferring methods has been the subject of numerous investigations. This study approaches the problem from a less discussed point of view, i.e. the effect of different surgical techniques on body temperature changes. METHODS: Body temperature was measured at 3 core and 6 skin points in 40 patients scheduled for cholecystectomy through open laparotomy or laparoscopy with pneumoperitoneum created and maintained with unwarmed carbon dioxide (CO2) insufflation. End-tidal CO2 was kept constant by adjustments of respiratory frequency. Anaesthesia, intravenous infusions, and draping of the patients were standardized. RESULTS: During the first 1 h of anaesthesia core temperatures decreased approximately by 0.7 degrees C and distal skin temperatures increased by 7 degrees C in both groups. At the end of surgery heat balance was similar in both groups. An increase of 2.5 1.min-1 in respiratory minute volume was needed to control end-tidal CO2 levels in the laparoscopy group during pneumoperitoneum which was maintained with a CO2 flow of 1.2 1.min-1 through the abdominal cavity. CONCLUSION: Laparoscopic technique with unwarmed carbon dioxide insufflation does not offer any advantage in terms of body temperature changes when compared to open surgery.     

The role of integrins and extracellular matrix in anchorage-independent growth of a mammary carcinoma cell line

Anchorage-independent growth is a property of malignant cells. Extracellular matrix proteins are present in tumor spheroids but their function is not clearly defined. In this paper we show that a murine mammary carcinoma cell line, SP1, which expresses the fibronectin receptor alpha 5 beta 1 requires fibronectin for anchorage-independent growth in soft agar. Growth factors (hepatocyte growth factor and transforming growth factor-beta) also promote SP1 colony growth. In contrast, collagen types I and IV have an inhibitory effect on SP1 colony growth. A clone isolated from SP1 cells which expresses the collagen/laminin receptor alpha 2 beta 1 as well as the fibronectin receptor alpha 5 beta 1, demonstrates increased colony formation in the presence of fibronectin and collagen. These data suggest a role for both the alpha 5 beta 1 and alpha 2 beta 1 integrin receptors in the regulation of anchorage-independent growth of mammary carcinoma cells.     

Biochemical and functional characterization of recombinant von Willebrand factor produced on a large scale

Recombinant von Willebrand factor (r-vWF) was produced in serum-free medium on a large scale in recombinant Chinese hamster ovary cells and was purified from fermentation supernatant by a combination of anion exchange chromatography and heparin affinity chromatography. Heparin affinity chromatography yielded r-vWF polymers of different degrees of multimerization. r-vWF was analysed by qualitative and quantitative functional analysis. We could show that while binding of r-vWF to platelets did not depend on multimerization of the molecule, ristocetin-induced platelet aggregation, binding to collagen and binding to heparin correlated directly with the extent of multimerization. Binding of recombinant coagulation factor VIII (r-FVIII) to r-vWF was studied by real-time biospecific interaction analysis and surface plasmon technology. The data indicated that binding of r-FVIII did not depend on r-vWF multimerization. Real-time biospecific interaction analysis suggested a potential stoichiometry of 2 to 2.5 r-vWF subunits per r-FVIII molecule. Kinetic analysis of the r-vWF-r-FVIII interaction gave a binding rate constant of 3 x 10(6) M-1 s-1 and an association constant of 2.5 x 10(9) M-1. Reaction of r-vWF with carbohydrate-specific lectins demonstrated that r-vWF contained a high proportion of N-glycans composed of mannose, galactose, glucose, N-acetylglucosamine and terminal sialic acid. Carbohydrate moities were covalently bound to the protein structure and were quantitatively removed from r-vWF only after protein denaturation. The results demonstrated that r-vWF produced on large scale under serum-free culture conditions exhibited qualitative and quantitative functional properties comparable to human plasma-derived vWF.     

Localization and characterization of a chromosome 11 tumor suppressor gene using organotypic raft cultures

The development and progression of human cancer often involves the inactivation of tumor suppressor gene function. Alterations in human chromosome 11 during the development of human cutaneous squamous cell carcinoma suggest the presence of a tumor suppressor gene on this chromosome. Moreover, previous studies in our laboratory demonstrated the presence of a functional tumor suppressor gene on chromosome 11 for the human cutaneous squamous cell carcinoma cell line A388.6TG.c2. In this investigation, we have used organotypic culturing of epithelial cells as a novel in vitro assay for tumor suppression. A388.6TG.c2 and control cells form an abnormal stratified epithelium of 8-12 layers when cultivated on organotypic rafts. In contrast, the chromosome 11 microcell hybrids, HMC 100p4B and HMC 100p5A, form an epithelium of only two to three cell layers. This in vitro growth suppression of the chromosome 11 microcell hybrids in the organotypic rafts correlates well with our previous in vivo skin graft experiments. Comparison of the proliferation and apoptotic indices of cell lines grown on the organotypic rafts suggests that the tumor suppressor gene on chromosome 11 has restricted the ability of the microcell hybrids to stratify but has not significantly altered their ability to undergo cell division or programmed cell death. Furthermore, flow cytometric analysis of cells grown on organotypic raft cultures suggests that the chromosome 11 microcell hybrids are actively progressing through the cell cycle rather than arrested in a particular stage. We have used this novel application of organotypic raft cultures to further localize the chromosome 11 tumor suppressor gene. Introduction of a single der(11)t(X;11) chromosome lacking most of the long arm of chromosome 11 into A388.6TG.c2 does not affect growth on organotypic raft cultures. These data suggest the tumor suppressor gene maps to the long arm of chromosome 11 in the region of 11q13-qter.