Biomedical subjects
Publications and source records attributed to M Pfaff.
NURSETALK is an electronic bulletin board system (BBS) developed to provide information and meet the communication needs of three different nursing organizations in North Carolina. It was designed and conceptualized from a user perspective to promote functionality and acceptance.
Only two out of three ideal types of health care systems can be observed in the European Community (EC): Centrally planned systems (countries with a national health service) and systems managed mainly by associations of health insurance funds and also of providers (countries with a social insurance system). We find no country with a market-type health care system in Europe. Both types of systems occurring in the EC are compared with each other, both with regard to their ideal types and also to their actual operations when judged on grounds of financing and production of health care. When seen as ideal types, we note considerable differences. Real types however exhibit only gradual differences. The shares of major subcategories of health spending differ widely between EC countries. These differences, however, cannot be attributed to the different health care systems. Similar observations can be made regarding different forms of payment for hospital care and for physician services and also regarding the share of total health expenditure in GDP.
Pepsin-solubilized collagen VI in triple-helical and heat-denatured, unfolded form was shown to promote Mg(2+)- and Mn(2+)-dependent attachment and spreading of various cell lines. On the triple-helical substrate no inhibition of cell adhesion was observed with several synthetic RGD peptides except in the case of A375 melanoma cells. In contrast, adhesion to the unfolded substrate was highly sensitive to RGD inhibition. Nine synthetic peptides were designed according to 10 RGD sequences present in the triple-helical sequence of human collagen alpha 1(VI), alpha 2(VI), and alpha 3(VI) chains. Only one peptide, corresponding to the C-terminal end of alpha 3(VI) chain, showed substantial inhibitory activity, whereas several peptides were active in direct adhesion assays when used as albumin conjugates. Inhibition tests with antibodies to integrin subunits, affinity chromatography, and ligand binding with purified integrins (alpha 1 beta 1, alpha 2 beta 1, alpha V beta 3, and alpha IIb beta 3) were used to identify collagen VI receptors. Binding to the triple-helical substrate is mediated by alpha 1 beta 1 and alpha 2 beta 1 integrins. Binding of both integrins to collagen VI was weaker than that to collagens I and/or IV. Recognition of the denatured substrate is mediated by beta 1 and beta 3 integrins. Activity was shown for alpha 5 beta 1 and alpha V beta 3 and weakly for alpha IIb beta 3 but not all alpha subunits possibly involved were identified. Distinct sets of receptors were also involved in A375 cell binding to triple-helical (beta 1-mediated) and denatured (beta 3-mediated) collagen VI, even though in this case both interactions could be efficiently inhibited by RGD peptides.
Four well differentiated gastric adenocarcinoma cell lines from German patients have been established from primary tumors (St 23132, St 3051) and lymph node metastases (St 2474, St 2957). The tumor cells were isolated by enzymatic or mechanical treatment. All four lines grew as solid tumors in nude mice and formed colonies in soft agar. The doubling time of the cells in culture was 25-32 h. Further characteristics of the lines were a considerable chromosomal aneuploidy, (the chromosomal numbers varying from 30-109 with many numerical and structural abnormalities), a stable keratin expression (Ck 8, 18, 19), the expression and secretion of CEA and CA-19-9 and the overexpression of c-myc. The four stomach cancer cell lines described here are not only a useful addition to the small number of existing lines, but also represent ideal tools for studying tumorigenicity of human stomach cancers in vitro and in vivo.
For a comparative study of the humoral immunity of patients with gastric signet-ring cell carcinoma, lymphocytes from spleen and lymph nodes were fused with the heteromyeloma SPM4-0. Immunoglobulin-producing clones were primarily tested in binding assays on autologous and allogeneic tumor cells and tissues. One of the resulting human monoclonal antibodies, designated 56/16 (IgM, lambda), was found to be suitable for a detailed biochemical characterization. Immunoblotting and comparative two-dimensional gel electrophoresis on cell and tissue extracts as well as on preparations of the cytoskeleton revealed that the main epitope is not an integral membrane molecule but a degradation product of cytokeratin 8, which is a main component of the tumor marker, tissue polypeptide antigen. The Mr 38,000/45,000 antigen could be identified in tumor and normal tissues, with highest expression in secretory cells and organs. Thus, the human monoclonal antibody 56/16 might represent an immune response in the patient against breakdown products of cytokeratin 8, which are released from the tumor cells during cell division, secretion, or cell death. A possible association of the antibody with the secretory activity of signet-ring carcinoma cells is discussed.
To obtain suitable cell lines for the immortalisation of human lymphocytes, we constructed a heteromyeloma between the murine myeloma Ag8 and human lymphocytes from a highly malignant polymorphic, centroblastic B-cell lymphoma. The thioguanine-resistant and HAT-sensitive heteromyeloma HAB-1 neither secretes nor contains cytoplasmatic immunoglobulins, the cells being EBV negative but positively stained for HLA-BC and the human proliferation marker Ki-67. The karyotype consists of about 50 murine and 20 human chromosomes. The HAB-1 cells grow in suspension and have a doubling rate of about 25-30 h. In fusion experiments with spleen cells from stomach carcinoma patients HAB-1 cells show a 5-7 times higher fusion efficiency than murine Ag8 cells or another heteromyeloma SPM4-0 and give stable antibody producing products. The cell line will be made available to interested scientists.
The empirical evidence available for OECD countries suggests that economic factors play a major role and that demographic factors play a minor role in explaining differences in health care spending across countries. When countries are grouped on the basis of their health care systems, some significant cross-country differences result: countries with higher transfer rates (a larger share of collective financing) are not generally characterized by higher health care expenditures, and conversely, countries with a larger share of private financing (including higher coinsurance rates) do not have lower expenditures. Rather, the opposite holds true. Similar conclusions apply to the share of public versus private production of health goods. Furthermore, the results do not support the claims of those critics of universal public insurance systems who consider the expansion of the coverage to be a major source of expenditure growth. These findings cast serious doubt on the claim that cost containment can be achieved via market reforms that rely heavily on direct consumer payments and cost sharing as instruments of financing. A comparative analysis of the historic record of the United States, Canada, and the Federal Republic of Germany generally supports these conclusions; it also suggests that a greater degree of public penetration offers a better chance for control of health spending, particularly in periods of austerity. There is a strong presumption that health care systems relying on some overall control of spending generally are more cost-effective than those relying more on decentralized mechanisms of control. Services are more equitably distributed in relation to health and payment for health services is far more progressive in the former type of system.
Administration of the photoactivable compound chlorpromazine (CPZ) to SKH-1 hairless mice via their drinking water (CPZ, 0.01%) significantly reduced the rates of accumulation and yields of squamous cell carcinomas induced by long-term repeated exposures of these animals to solar UV radiation. This protective effect of CPZ was partially reversed in mice given a single injection of ethyl nitrosourea at birth. In in vitro studies, the presence of CPZ (0.2 mM) in mammalian cell cultures enhanced the yield of DNA single-strand breaks induced in the cells by exposure to monochromatic UVA radiation at 334 nm. Collectively, the results suggest that CPZ may exert antineoplastic effects against UV-induced skin tumours by the induction of DNA damage.
In STU mice bearing metastasizing SV40-transformed 51A-232B-M tumors, an immune response against a cellular 60kDa protein (p60) developed in about 50% of the tumor-bearing animals, in addition to the response against SV40 large T-antigen and cellular protein p53. The anti-p60 auto-immune response could be observed as early as 11 days after tumor challenge and was strictly linked with metastatic spread but was not a prerequisite for metastasis. Anti-p60 antibodies could not be detected in sera of animals bearing metastasizing Rous-sarcoma virus-transformed or methylcholanthrene-induced tumors, or in sera from human cancer patients with clinically confirmed metastatic spread. The anti-p60 auto-antibodies showed a broad cross-reactivity against components of similar size in a great number of cell lines of various species and in normal mouse tissue. The p60 auto-antigen is a cytoplasmic protein which is neither phosphorylated nor glycosylated in vivo. Immunoblotting performed with fresh cell lysates under non-reducing conditions using tumor-bearer sera revealed a diffuse p60 double band, but under reducing conditions only one sharp p60 band was observed. The reaction of p60 with anti-p60 auto-antibodies could be completely blocked by pre-treatment of fresh cell lysates with N-ethylmaleimide or p-chloromercuriphenyl sulfonate, or by oxidation in air prior to immunoblotting, indicating that the anti-p60 autoimmune response was directed against an epitope sensitive to SH-group-blocking reagents. Immunofluorescence studies with tumor-bearer sera showed only a very weak cytoplasmic fluorescence, possibly due to the nature of the p60 SH-groups in situ being masked. Immunoprecipitates with monoclonal antibodies against SV40 large T-antigen and p53 obtained from fresh cell lysates of SV40-transformed tumor cells contained no associated p60 auto-antigen. The p60 auto-antigen was purified from tumor cell homogenates with an enrichment factor of about 2,000; its iso-electric point is at pH 6.8. Determination of the biological half-life of p60 yielded a value of about 28 hr. The p60 auto-antibodies in pools of tumor-bearer sera taken at day 40 after tumor challenge all belonged to the IgG1 subclass.
A rabbit antiserum against highly purified casein kinase II from mouse tumor cells was used for immunolocalization of the enzyme in fixed, permeabilized mouse cells. Casein kinase II was highly accumulated in nucleoli compared to the extra-nucleolar space of the nucleus or to the cytoplasma. Casein kinase II samples highly purified from the cytoplasma, from the extra-nucleolar fraction of the nucleus or from nucleoli exhibited no differences with respect to structure and function. All samples originally had an alpha 2 beta 2 structure (alpha, 42 kDa; beta, 24 kDa) showing formation of the alpha'-chain (36 kDa) only in the late steps of purification. The isoelectric point of the alpha-chain of all three samples was pH 7.7 and that of the beta-chain was pH 6.4-6.6. Using ATP or GTP, all three casein kinase II samples gave the same results of maximum phosphorylation of purified nucleolar marker phosphoproteins pp105/C23, pp135 and B23, yielding pp135 as one of the most highly phosphorylated proteins with an incorporation of about 75 phosphate groups per molecule pp135. Studies on optimum conditions of phosphorylation of nucleolar phosphoproteins by casein kinase II revealed that each of the protein substrates individually responded to alterations of assay parameters such as pH, magnesium ion and sodium chloride concentrations indicating that predominantly individual structural criteria were responsible for optimum phosphorylation. The determination of the apparent Km of casein kinase II for purified nucleolar phosphoproteins yielded values of 0.15 microM (pp105/C23), 0.1 microM (pp135) and 1.0 microM (B23) identifying them as high-affinity substrates of casein kinase II.
Subjective interpretation of angiographic left ventricular regional wall motion is routinely performed with knowledge of the location and extent of coronary artery stenosis. We studied 100 patients with coronary artery disease in order to determine the accuracy of such wall motion assessment relative to a more objective standard based upon computer-assisted left ventricular (LV) ejection fraction and end-systolic fractional shortening referenced to the end-diastolic area centroid. Only 379 of 700 (54%) region-by-region comparisons of wall motion were in precise agreement. Computer-assisted wall motion analysis correlated significantly better with ejection fraction than did subjective analysis (r = 0.82 vs r = 0.61, p less than 0.002). In 56 patients, in whom major discordance was noted, subjective assessment of wall motion correlated significantly better with the presence of coronary artery stenosis (p less than 0.05), but objective assessment correlated significantly better with ejection fraction in these same patients (p less than 0.02). These data suggest that the accuracy of subjective assessment of regional wall motion, relative to global ejection fraction, can be adversely biased by knowledge of the patient's coronary anatomy. Because of the inherently reproducible nature of the algorithmic process, and in light of the better correlation with global function, computer-assisted analysis of regional wall motion might be preferable to conventional subjective assessment.
Adrenal effluent concentrations of aldosterone were measured along with testosterone, androstenedione, and cortisol in 17 women with idiopathic hirsutism. In the basal state, aldosterone secretion (higher concentrations vs peripheral blood) was demonstrated in 14 out of 16 of the women, in contrast to 8 out of 16 who demonstrated cortisol gradients. Nine women received 0.25 mgm beta 1-24 ACTH im and serial adrenal venous blood samples were obtained over the next 30 minutes. Parallel 30-40-fold increments were noted in aldosterone, androstenedione, and cortisol; testosterone increased only 8-fold. These marked changes in adrenal effluents were not observed in simultaneously monitored peripheral blood. Minimal changes in these steroid concentrations were noted in adrenal and peripheral blood in 7 women who received 2,000 IU hCG. One woman received a pressor dose of angiotensin II, resulting in a marked increase in adrenal vein aldosterone and a simultaneous decrease in cortisol. Since adrenal androgen secretion parallels cortisol, quantification of adrenal androgen secretion rates can be achieved by sampling the adrenal effluent and relating the androgen gradient to that of cortisol at any given time. In contrast, aldosterone secretion is often independent of cortisol, and thus cannot be estimated by comparison of adrenal gradients. ACTH administration, however, invariably stimulated aldosterone secretion, enabling us to quantify the "ACTH-related aldosterone secretion rate" from a comparison of maximal adrenal gradients of aldosterone vs cortisol. In 6 women, "ACTH-related aldosterone" secretion rate averaged 40 mug/day, roughly 20% of the total daily aldosterone secretion rate.
The last 40 years has been a time of rapid demographic, social and economic change in most countries of the world. In Europe, the ageing of the population, a decrease in household size, and the reduced importance of parasitic and infectious diseases along with an increase in chronic and degenerative diseases are some of the most notable results of industrialization, urbanization and medical progress. These developments lead to changing demands not only for the services of hospitals but upon the health care system at large. Most recently, and in addition, these changes have had to be faced under resource constraints resulting from decreased economic growth. This article focuses on the similarities and differences within and across the health care systems of European countries, and on their efforts to respond to the changes which have taken place and are likely to continue in the near future. In so doing, it relates the various demographic, social and economic changes taking place in these countries to the structural changes noticeable in the hospital sector. The results obtained by statistical analyses of empirical evidence lead us to conclude that demographic and social variables may better explain the differences in hospital use within a given country over longer stretches of time than across countries at a given point in time. In the latter case, economic variables--differences in gross domestic product (GDP) per capita--serve as major explanations of the cross-country differences found. Changes in demographic, social and morbidity factors are also mirrored in the relative importance of hospital departments, at a given point in time and also in changes over time. Major changes have taken place within the health care systems. Hospitals are losing ground to other forms of health care: for instance, to institutions providing pre-hospital and post-hospital treatment. The need for more caring patterns of service, rather than for more curing, accounts for yet another overall trend. Hospitals have started to respond to this need by offering more 'semi-stationary' and part-time health care facilities. These developments go hand in hand with the establishment of closer relations between hospitals and other facilities within the health care system, and with improved non-stationary health care services.
The purpose of this study was to describe a method to quantify dynamic patellar tracking using kinematic MRI (KMRI). Twelve normal females and three patients with patellofemoral pain participated. Imaging was performed with a 1.5-T/64-MHz MR system using a fast spoiled gradient-recalled acquisition in the steady state (GRASS) pulse sequence. A nonferromagnetic positioning device permitted active, bilateral knee extension against resistance (15% bwt) from 45 degrees knee flexion to full extension. Subjects were instructed to extend their knees at a rate of 9 degrees per second, which allowed images to be obtained at 45 degrees, 36 degrees, 27 degrees, 18 degrees, 9 degrees, and 0 degrees. All images were assessed for medial/lateral patellar displacement, patellar tilt, and sulcus angle using a computer-aided system. Normal patellar motion was characterized by medial movement from 45 degrees to 18 degrees, followed by a reversal toward lateral displacement from 18 degrees to full extension. The results for patellar tilt revealed a tendency toward decreasing lateral tilt as the knee extended. Sulcus angle measurements indicated that the patella was moving to a more shallow portion of the trochlear groove (superiorly) during extension.