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Reduced phagocytosis of apoptotic cells in malignant lymphoma.

Efficient removal of lymphocytes undergoing programmed cell death (apoptosis) by macrophages plays an important role for the proper function of normal immune system. Furthermore, in malignant lymphoma, elimination of apoptotic tumor cells by phagocytes contributes to the anti-tumor immune response. It is unknown, however, whether macrophages in normal and malignant lymphoid tissues differ in their ability to recognize and remove apoptotic cells. Our present results demonstrate that normal and malignant lymphoid tissues differ according to the extent of the infiltration by macrophages. The highest densities of macrophages (p < 0.0001) were detected in diffuse large B-cell lymphoma, centroblastic (DLBCL-CB) and immunoblastic variants and Burkitt's lymphoma. The grade of the macrophage infiltration correlated with the proliferation rates of the tumors (p < 0.0001). Compared with normal lymphoid organs, malignant lymphoma contained lower percentages of apoptotic cells phagocytosed by tissue macrophages (p < 0.001). Of all lymphomas tested, mantle cell lymphoma and DLBCL-CB expressed the lowest percentages of phagocytosed apoptotic cells (p < 0.0001).

Apoptosis↗

Principles of early detection of cancer.

Screening for the early detection of cancer offers the potential of increasing the number of patients whose cancer is diagnosed in a localized, curable stage. The operation of an efficient and effective early detection program requires that a number of conditions be fulfilled, some of which are difficult to attain. First, the target population for screening should be defined demographically and epidemiologically so that the screening program is designed to be responsive to the needs of that group, e.g., age, ethnic composition, special occupational or environmental circumstances. Furthermore, an appropriate means of communicating with the reference population must be established so that the group can be educated regarding cancer prevention and detection and motivated to use early detection programs. Screening for early detection should be carried out on two levels: primary screening for the identification of risk factors, and prescriptive screening for additional procedures ordered according to the patterns of risk factors, and prescriptive screening for additional procedures ordered according to the patterns of risk factors identified. The screening encounter should be an opportunity for health education regarding primary prevention, as well as early detection of cancer. Screening without follow-up for diagnosis and treatment is likely to be counterproductive; the patient must be provided with a means of entering the health care system when this is indicated by the screening examination. Follow-up of suspicious findings must also be carried out for end-result evaluation. Primary screening can be carried out successfully by allied health personnel under most circumstances. A program employing these principles is now being utilized by a number of independent clinics in a voluntary collaborative program called "CANSCREEN." Examples of the operational modes of this program will be presented.

Community Health Centers↗

Oncoprotein 18 levels and phosphorylation mediate megakaryocyte polyploidization in human erythroleukemia cells.

Megakaryocytes undergo an unusual cell cycle during differentiation that results in polyploidy through largely unknown mechanism(s). It has been shown that serine phosphorylation of oncoprotein 18 (Op18) is required for cell cycle progression specifically at the G2/M transition. Moreover, mutant forms of Op18 that are defective in one or more of the four serine residues induce G2/M arrest and subsequent polyploidization. Op18 phosphorylation is rapidly induced with phorbol myristate acetate (PMA) treatment in a wide range of human cells. In this study, we investigated the role of Op18 in PMA induced polyploidization during megakaryocyte differentiation of the human erythroleukemia cell line. Crucial to the molecular analysis of megakaryocyte differentiation, is the ability to fractionate cell populations with different ploidy levels. We have utilized cell elutriation as a fractionation strategy to analyze Op18 expression in synchronized cell subpopulations in different phases of the cell cycle or with progressive megakaryocyte polyploidization. In the absence of PMA, increased phosphorylation of Op18 was observed in HEL cells during cell cycle progression, as for other proliferating cells. However, in contrast to Jurkat leukemia cells chosen as control, HEL cells exhibited a lack of Op18 phosphorylation in response to PMA, which was accompanied by polyploidization and differentiation along the megakaryocytic lineage. To further determine the role of Op18 in polyploidization, HEL cells were transfected with different Op18 expression constructs. Differences in cell survival and polyploidization were observed between high and low Op18 expressors. An increased Op18 level reduced cell survival during the early stage of PMA induced megakaryocyte differentiation, but enhanced polyploidization efficiency. Our findings suggest that maintenance of a high level of unphosphorylated Op18 is required for efficient polyploidization during the differentiation program of megakaryocytes.

Cell Cycle↗

Designing education interventions to improve physician performance in office practice.

Family doctors play a very important role in determining the health of the populace; however, surveys and expert opinions indicate that there is considerable room for improvement in the knowledge and skills of family physicians concerning the prevention, early detection and management of the major causes of death and disability. Effective Continuing Medical Education (CME) could help greatly to resolve this problem. THere is, however, little evidence that presently available systems of CME, though costly, are effective in improving either physician competence or patient health. Attractive and cost-effective CME methods are greatly needed. This study develops, field tests and evaluates more efficient office-based CME programs for family doctors. Prevention, early detection and improved management of cardiovascular disease and cancer are the primary goals. A pretest posttest control group and time series approach was chosen for the experimental design. Thirty-one family physicians are participating. Physician performance and patient outcome prior to and after education are being assessed largely through office record review.

Education, Medical, Continuing↗

A proposal for cervical screening information systems in developing countries.

The effective and efficient delivery of cervical screening programs requires information for planning, management, delivery and evaluation. Specially designed systems are generally required to meet these needs. In many developing countries, lack of information systems constitutes an important barrier to development of comprehensive screening programs and the effective control of cervical cancer. Our report outlines a framework for creating such systems in developing countries and describes a conceptual model for a cervical screening information system. The proposed system is modular, recognizing that there will be considerable between-region heterogeneity in current status and priorities. The proposed system is centered on modules that would allow for the assembly and computerization of data on Pap tests, since these represent the main screening modality at the present time. Additional modules would process data and create and maintain a screening database (e.g., standardize, edit, link and update modules) and allow for the integration of other types of data, such as cervical histopathology results. An open systems development model is proposed, since it is most compatible with the goals of local stakeholder involvement and capacity-building.

Databases as Topic↗

OOPSE: an object-oriented parallel simulation engine for molecular dynamics.

OOPSE is a new molecular dynamics simulation program that is capable of efficiently integrating equations of motion for atom types with orientational degrees of freedom (e.g. "sticky" atoms and point dipoles). Transition metals can also be simulated using the embedded atom method (EAM) potential included in the code. Parallel simulations are carried out using the force-based decomposition method. Simulations are specified using a very simple C-based meta-data language. A number of advanced integrators are included, and the basic integrator for orientational dynamics provides substantial improvements over older quaternion-based schemes.

Journal Article↗

The assessment of child abuse potential and the prevention of child abuse and neglect: a policy analysis.

A frequently advocated strategy for increasing the efficiency of child abuse prevention programs is to deliver prevention services to "high-risk" populations. This article critically reviews procedures for the reliable and valid assessment of child abuse potential within an ecological perspective. Factors that limit the usefulness of child abuse risk assessment are discussed. These factors include the uncertain criteria of child abuse and neglect, the low base rate of the phenomenon, and the financial and social costs of such procedures. Finally, the prevention implications of the current and future state of the art in child abuse risk assessment are considered and preventive interventions that do not depend on individual case risk screening are advocated.

Child↗

[Occupational medicine preventive studies in West Germany].

Prevention is of increasing importance in medicine, particularly in occupational medicine. The programs of health surveillance at the workplace in the Federal Republic of Germany are discussed. In 1983, 1,400,000 examinations of employees were performed; exclusion criteria were fulfilled in 2.1% (0.9% only temporarily). In 1984 the respective numbers were 1,450,000 examinations (1.8%, 0.8%). During the last few years, health surveillance programs markedly have improved the efficiency of prevention of occupational diseases. They will be an important task for occupational physicians in the future.

Cost-Benefit Analysis↗

Translational regulation by modifications of the elongation factor Tu.

EF-Tu from E. coli, one of the superfamily of GTPase switch proteins, plays a central role in the fast and accurate delivery of aminoacyl-tRNAs to the translating ribosome. An overview is given about the regulatory effects of methylation, phosphorylation and phage-induced cleavage of EF-Tu on its function. During exponential growth, EF-Tu becomes monomethylated at Lys56 which is converted to Me2Lys upon entering the stationary phase. Lys56 is in the GTPase switch-1 region (residues 49-62), a strongly conserved site involved in interactions with the nucleotide and the 5' end of tRNA. Methylation was found to attenuate GTP hydrolysis and may thus enhance translational accuracy. In vivo 5-10% of EF-Tu is phosphorylated at Thr382 by a ribosome-associated kinase. In EF-Tu-GTP, Thr382 in domain 3 has a strategic position in the interface with domain 1; it is hydrogen-bonded to Glu117 that takes part in the switch-2 mechanism, and is close to the T-stem binding site of the tRNA, in a region known for many kirromycin-resistance mutations. Phosphorylation is enhanced by EF-Ts, but inhibited by kirromycin. In reverse, phosphorylated EF-Tu has an increased affinity for EF-Ts, does not bind kirromycin and can no longer bind aminoacyi tRNA. The in vivo role of this reversible modification is still a matter of speculation. T4 infection of E. coli may trigger a phase-exclusion mechanism by activation of Lit, a host-encoded proteinase. As a result, EF-Tu is cleaved site-specifically between Gly59-Ile60 in the switch-1 region. Translation was found to drop beyond a minimum level. Interestingly, the identical sequence in the related EF-G appeared to remain fully intact. Although the Lit cleavage-mechanism may eventually lead to programmed cell death, the very efficient prevention of phage multiplication may be caused by a novel mechanism of in cis inhibition of late T4 mRNA translation.

Escherichia coli↗

QTL and candidate genes phytoene synthase and zeta-carotene desaturase associated with the accumulation of carotenoids in maize.

Carotenoids are a class of fat-soluble antioxidant vitamin compounds present in maize ( Zea mays L.) that may provide health benefits to animals or humans. Four carotenoid compounds are predominant in maize grain: beta-carotene, beta-cryptoxanthin, zeaxanthin, and lutein. Although beta-carotene has the highest pro-vitamin A activity, it is present in a relatively low concentration in maize kernels. We set out to identify quantitative trait loci (QTL) affecting carotenoid accumulation in maize kernels. Two sets of segregating families were evaluated-a set of F2:3 lines derived from a cross of W64a x A632, and their testcross progeny with AE335. Molecular markers were evaluated on the F2:3 lines and a genetic linkage map created. High-performance liquid chromatography was performed to measure beta-carotene, beta-cryptoxanthin, zeaxanthin, and lutein on both sets of materials. Composite interval mapping identified chromosome regions with QTL for one or more individual carotenoids in the per se and testcross progenies. Notably QTL in the per se population map to regions with candidate genes, yellow 1 and viviparous 9, which may be responsible for quantitative variation in carotenoids. The yellow 1 gene maps to chromosome six and is associated with phytoene synthase, the enzyme catalyzing the first dedicated step in the carotenoid biosynthetic pathway. The viviparous 9 gene maps to chromosome seven and is associated with zeta-carotene desaturase, an enzyme catalyzing an early step in the carotenoid biosynthetic pathway. If the QTL identified in this study are confirmed, particularly those associated with candidates genes, they could be used in an efficient marker-assisted selection program to facilitate increasing levels of carotenoids in maize grain.

Alkyl and Aryl Transferases↗

Resolution of the essential constituents of Ramulus cinnamomi by an evolving chemometric approach.

The analysis of complex mixtures, such as those of traditional Chinese medicine (TCM), is difficult by conventional methods of analysis. Chemometric methods provide a new way to solve such problems. Subwindow factor analysis (SFA) paired with the evolving window orthogonal projection (EWOP) method, has been used as a new evolving approach to the resolution of volatile components of Ramulus cinnamomi (RC). Compared with conventional chromatographic analysis, the chromatographic separation conditions necessary are greatly mitigated in our approach, yet the accuracy of qualitative and quantitative results is improved, because the measured data matrix has been resolved into chromatograms and mass spectra of the chemical components. Our method is, moreover, friendly to use and easy to program. Experimental results show the efficiency and convenience of the proposed approach. Forty-seven of the seventy-eight separated constituents in an essential oil, accounting for 89.55% of the sample, were identified by mass spectroscopy (MS).

Chromatography↗

Diversifying microbial natural products for drug discovery.

Historically, nature has provided the source for the majority of the drugs in use today. More than 20,000 microbial secondary metabolites have been described, but only a small percentage of these have been carried forward as natural product drugs. Natural products are in tough competition with large chemical libraries and with combinatorial chemistries. Hence, each step of a natural product program has to be more efficient than ever, starting from the collection of environmental samples and the selection of strains, to metabolic expression, genetic exploitation, sample preparation and chemical dereplication. This review will focus on approaches for diversifying microbial natural product strains and extract libraries, while decreasing genetic and chemical redundancy.

Bacteria↗

A sphere-based descriptor for matching protein structures.

This paper describes the use of a descriptor based on the number of alpha-carbon atoms within a sphere centered on the alpha-carbon in each amino acid residue in a protein. The descriptor can be used instead of the residue types in a dynamic programming algorithm, thus providing an efficient way of aligning protein structures. The method is applied to the alignment of protein families and to database searching. The results indicate that the method can quickly align protein sequences considering the 3D structure and can find proteins that are 3D structurally similar and dissimilar to the target protein.

Amino Acid Sequence↗

Human papillomavirus in cervical cancer.

Epidemiologic studies supported by molecular technology have provided sufficient evidence of the causal role of some human papillomavirus (HPV) infections in the development of cervical cancer. The finding is consistent universally, and HPV has been proposed as the first identified necessary cause of cervical cancer. Such recognition translates into the concept that cervical cancer does not develop without persistent presence of HPV DNA. In the developed parts of the world, cytologic screening programs could benefit from the addition of HPV testing to their protocols. Controlled studies and one randomized trial have shown that HPV testing is helpful in solving the ambiguous cases generated by cytology reading. In populations where cytology programs are not functional or efficient, HPV testing is being evaluated as an alternative means of primary screening. Prevention of exposure to high-risk HPV types, either by prophylactic vaccination or by combined prophylactic and therapeutic immunologic intervention, may prove to be the most efficient and logistically feasible option for the prevention of cervical cancer in developing populations.

Age Distribution↗

Simultaneous repositioning of the maxilla, mandible, and chin. Treatment planning and analysis of soft tissues.

There is a clinical, biologic, and biomechanical foundation for simultaneous surgical repositioning of the maxilla, mandible, and chin in a significant proportion of adult and adolescent patients. The restoration of normal jaw function, optimal facial esthetics, and long-term stability are the sine qua non of successful orthognathic surgical procedures to simultaneously reposition the jaws. The key to the achievement of these objectives is to carefully and systematically analyze facial esthetics, establish esthetic priorities, and then coordinate and implement them through the use of cephalometric planning and occlusal studies. By meticulous and precise surgical technique, properly programmed, coordinated, and sequenced with efficient presurgical and postsurgical edgewise orthodontic therapy, and systematic postsurgical neuromuscular rehabilitation, the maxilla, mandible, and chin can be simultaneously repositioned with relatively few postoperative complications or sequelae. This article purposes to elucidate on the indications for two-jaw surgery and describe a simplified clinical-cephalometric analysis for orthognathic surgery. Representative case reports are presented and discussed to illustrate the esthetic, orthodontic, and surgical treatment objectives. The basic problems involved in diagnosis and treatment planning of patients who require two-jaw surgery are discussed as well.

Adolescent↗

New directions in scientific computing: impact of advances in microprocessor architecture and system design.

The new generation of microcomputers has brought computing power previously restricted to mainframe and supermini computers within the reach of individual scientific laboratories. Microcomputers can now provide computing speeds rivaling mainframes and computational accuracies exceeding those available in most computer centers. Inexpensive memory makes possible the transfer to microcomputers of software packages developed for mainframes and tested by years of experience. Combinations of high level languages and assembler subroutines permit the efficient design of specialized applications programs. Microprocessor architecture is approaching that of superminis, with coprocessors providing major contributions to computing power. The combined result of these developments is a major and perhaps revolutionary increase in the computing power now available to scientists.

Computers↗

Computer applications in thermoregulatory research.

Thermoregulatory information is a frequently used parameter in both physiological and psychophysiological research. Specific software programs using accepted formulae are not readily available to the scientist as is the hardware. The program described here uses the well-established physiological model by Burton, calculating mean skin temperature and mean body temperature. The primary goal of this microsoft Basic program is to aid the researcher through speed of execution and quantitative reliability. A few command alterations will allow this program to be used with most microcomputer systems currently available. The time saved using this program will greatly enhance the efficiency of the researcher's thermoregulatory data analyses.

Body Temperature↗

Anaerobic threshold.

The general interest in the application of exercise testing to evaluate the work capacity or change in the functional ability of individuals has resulted in the development of a variety of non-invasive tests and test parameters such as the anaerobic threshold. This paper presents a computer program written in BASIC that determines the anaerobic threshold from expired respiratory gases collected from an incremental exercise test. Results are summarized in tabular as well as graphical format. The use of the incremental exercise test in conjunction with this computer program provide another means of efficiently determining the exercise capability of the patient.

Algorithms↗