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In this study on motivations concerning professional development (PD) we interviewed 95 primary school teachers in the Netherlands. We coded these data using the Unified Model of Task-specific Motivation (de Brabander & Martens, 2014) in different decision contexts concerning who decides about teacher participation in PD: school board, teacher teams, or individual teachers. We analysed the valences that teachers associated with PD activities, their experiences of autonomy, and whether and how these variables were affected by decision context and teacher age. Results show that decision contexts relate differently to valences and autonomy experiences. Positive autonomy and positive valences increased going from schoolboard to team to individual decision contexts. Whereas the literature on effective teacher PD stresses the importance of PD design features, our study is the first to empirically demonstrate the crucial influence of decision contexts. Among older teachers, teaching experience informed the selection of PD content to transfer to their classrooms. Younger teachers tended to first explore whether PD worked in their classrooms before deciding about adoption. Direct applicability emerged as a dominant criterion for evaluating PD. Decision context and autonomy regarding PD programmes play important roles in ensuring applicability. Our research revealed that the dominance of the direct applicability criterion was not motivated by student benefits alone. It was also based in an attitude of efficiency among primary teachers, reflecting growing work pressures and a general prioritisation of classroom teaching above all other tasks, including PD.

This study explored the readiness of teachers to learn about learning and teaching supportive modes of ICT use with the lens of the Unified Model of Task-specific Motivation (UMTM). According to the UMTM readiness for action is driven by feelings of activities and thoughts about the value of consequences of activities, which both can be positive and negative, and which in turn are influenced by aspects of autonomy and competence, by social relatedness, and by subjective norm. The twofold goal of this study was to test the merits of the model in general and for ICT integration in education in particular. A sample of 282 teachers provided answers about different aspects of their motivation to learn about the two types of ICT use. There were some differences between these two types of learning activities, but for both, thoughts about the value of the consequences of the activities were more important than feelings about them. Furthermore, although sense of competence was relatively more important for leaning about learning supportive ICT use than for learning about teaching supportive ICT use, teachers’ sense of autonomy, a variable that is completely ignored in research on ICT integration, was in general far more important for learning about ICT use than sense of competence.

Background: Detecting SARS-CoV-2 antibodies may help to diagnose COVID-19. Head-to-head validation of different types of immunoassays in well-characterized cohorts of hospitalized patients remains needed. Methods: We validated three chemiluminescence immunoassays (CLIAs) (Liaison, Elecsys, and Abbott) and one single molecule array assay (SIMOA) (Quanterix) for automated analyzers, one rapid immunoassay RIA (AllTest), and one ELISA (Wantai) in parallel in first samples from 126 PCR confirmed COVID-19 hospitalized patients and 158 pre-COVID-19 patients. Specificity of the AllTest was also tested in 106 patients with confirmed parasitic and dengue virus infections. Specificity of the Wantai assay was not tested due to limitations in sample volumes. Results: Overall sensitivity in first samples was 70.6 % for the Liaison, 71.4 % for the Elecsys, 75.4 % for the Abbott, 70.6 % for the Quanterix, 77.8 % for the AllTest, and 88.9 % for the Wantai assay, respectively. Sensitivity was between 77.4 % (Liaison) and 94.0 % (Wantai) after 10 dpso. No false positive results were observed for the Elecsys and Abbott assays. Specificity was 91.1 % for the Quanterix, 96.2 % for the Liaison, and 98.1 % for the AllTest assay, respectively. Conclusion: We conclude that low sensitivity of all immunoassays limits their use early after onset of illness in diagnosing COVID-19 in hospitalized patients. After 10 dpso, the Wantai ELISA has a relatively high sensitivity, followed by the point-of-care AllTest RIA that compares favorably with automated analyzer immunoassays.

The aim of this investigation was to explore the merits of the Unified Model of Task-specific Motivation (UMTM). As in this model task-specific components from several partly conflicting theories were integrated, this study constitutes an important contribution to the further development of consensus about motivation theory. Four relatively independent types of valences are the core of the UMTM. Affective and cognitive valences represent feelings while doing an activity and thoughts about the value of its consequences respectively; both types of valences can be positive and negative, hence calling for approach and avoidance motivation respectively. The interaction between these four categories of valences results in a valence expectation, which influences readiness for action. Valences in turn are influenced by four categories of task-specific antecedents, namely appraisals of autonomy, feasibility, and social relatedness, and subjective norm. The global question we tried to answer was to what extent motivational data on specific activities could be modeled in accordance with the UMTM and how different, specific activities affect the influence that the components of the model exert. Structural equation modeling of questionnaire responses of 335 teachers on all components of the model except negative valences with respect to three imaginary types of professional learning activities (formal training, personal study, and reflection on practice) revealed that characteristics of the task determine to what extent components of the model come into play. It is concluded that the model represents a first promising step towards reuniting conflicting theories of motivation.

Purpose To evaluate the efficacy, safety, and stability of a foldable angle-supported Acrysof Cachet phakic intraocular lens (pIOL) to correct moderate to high myopia and compare endothelial cell loss after iris-fixated Artisan and Artiflex pIOL implantation. Setting University Eye Clinic Maastricht, the Netherlands. Design Retrospective observational study. Methods Foldable angle-supported pIOL implantation for myopia ranging from −6.0 to −16.5 diopters (D) was done. Uncorrected (UDVA) and corrected (CDVA) distance visual acuity, spherical equivalent (SE), and adverse events were documented preoperatively and 6 months and 1 and 2 years postoperatively. Endothelial cell loss after implantation of the foldable angle-supported pIOL and iris-fixated pIOLs was compared 6 months and 1 and 2 years postoperatively. Results There were 158 eyes. The UDVA was equal to or more than 20/25 in 95% of eyes at 1 and 2 years postoperatively. The mean SE was −0.17 D ± 0.43 (SD) 2 years postoperatively. One patient developed pupil ovalization, resulting in explantation of the pIOL from both eyes. Acute endothelial cell loss in the foldable angle-supported pIOL group was −3.2% ± 0.7%, significantly higher than after iris-fixated pIOL implantation. Chronic endothelial cell loss from 6 to 24 months after surgery was −3.8% ± 0.7%. At the 2-year follow-up, the chronic endothelial cell loss in the foldable angle-supported pIOL group was not different than with iris-fixated pIOLs (P > .05). Conclusions The foldable angle-supported pIOL effectively corrected moderate to high myopia. However, acute surgical endothelial cell loss was significantly higher than with iris-fixated pIOLs. Financial Disclosure Dr. Nuijts is a consultant to Alcon Laboratories, Inc., Thea Pharma GmbH, and ASICO LLC; he has received study grants from Acufocus, Inc., Alcon Laboratories, Inc., Carl Zeiss Meditec AG, Ophtec BV, and Physiol S.A. No other author has a financial or proprietary interest in any material or method mentioned.

In this research we studied studentś use of motivational strategies as mediator between motivational beliefs and motivational engagement. Dutch students in pre-vocational secondary education (N = 3602, mean age 14) completed a self-report questionnaire on five motivational strategies (Environmental Control, Interest Enhancement, Self Consequating, Performance Self-talk, Mastery Self-talk); motivational beliefs (value attached to schoolwork, competence); and motivational engagement (pleasure, effort, persistence, achievement). A validation of the questionnaire showed a good fit. Structural equation modelling indicated that strategy-use partly mediates the relation between value, and effort and pleasure. Competence showed a weak direct relation with effort an pleasure. No result were found for achievement. Further implications of these findings for practical use and further research are discussed.

To prepare students for effective workplace learning, it is necessary to have insight into the contextual characteristics that affect students' developing interest. Aiming at students to become selfregulated learners, teachers should act as mindful coaches, encouraging their students to monitor the quality of collaborative group work. A field study was conducted within the context of a Computer Supported Collaborative Learning (CSCL) project fostering self-regulated learning. Students and teachers made use of an electronic instrument that assessed and visualised students' experiences of the quality of group learning over time. 137 vocational students in commerce and business administration participated in a 6 months project requiring to work in small learning groups. A SEM model, based on self-determination theory, fitted the data quite well. Perceived autonomy, competence, and social relatedness seemed to be good predictors of students' situational interest. Qualitative interview data revealed not only the added value of process-oriented reflection and within-group discussion, but also some shortcomings concerning the effectiveness of (implementing) CSCL.

To prepare students for instructive collaboration, it is necessary to have insight into students' psychological needs and interest development. The framework of self-determination theory was used to conduct a field experiment involving 114 students in vocational education. These students followed a practical business course which required they work in small learning groups. During the course, students were asked to complete the Quality of Working in Groups Instrument, an online measure of how strong autonomy, competence, social relatedness, and task interest are fulfilled. SEM showed that students' psychological needs were jointly and uniquely related to task interest over time. The significance of this on-line test for the assessment of interest within project-based education is discussed.

This study explored the relations between epistemological beliefs, social status of parents (n = 262), and school preferences. Epistemological beliefs were measured by 20 bi‐polar statements. School preferences were derived from paired comparisons of educational quality of available primary schools. Social status was measured in two dimensions, status level and status type, derived from parents' responses on life style. One dimension of a three‐dimensional unfolding solution of school preferences, interpreted as a contrast of old‐fashioned versus modern, was substantially related both to epistemological beliefs and to social status level. Though epistemological beliefs were related to level of education, their relation to status level and status type was not confirmed.

Corneal topography has, due to developments in refractive surgery and contact lens fitting, become a widely used diagnostic tool. Many types of topographers have been introduced, but there is some confusion on classification and subsequent principal possibilities of the various devices offered to the practitioner. The purpose of the study reported here was to make an inventory of developed devices, analyse the basic principles and create a classification based on optical principles. A literature search was done using Medline, the IBM Patent Server, and references found in articles and patents. This search resulted in a variety of descriptions that could be classified into 12 groups according to their use of light source and light-matter interaction of which four groups have representatives on the commercial market. This classification can be used by researchers and practitioners to gain insight into the possibilities of a given device in relation to the desired application.

In this study the perception of psychological needs and motivation in a student-centred and a teacher-centred learning environment are compared, using Self Determination Theory as a framework. The self-report Intrinsic Motivation Inventory was completed by 230 students (mean age 16.1 years) in pre-vocational secondary education. School records on absenteeism and achievement were also analysed. As predicted, multi-level analyses showed that students in the student-centred learning environment reported higher levels of perceived autonomy, competence, relatedness and motivation, measured by pleasure and effort. Furthermore, boys were less absent. Achievement shows no differences. These results suggest that a student-centred form of learning can be more beneficial for students’ motivation if granted autonomy is embedded in a supportive environment.

This study aims to integrate the current proliferation of motivation theories in a Unified Model of Task-specific Motivation (UMTM). According to this model readiness for action results from an interaction between four relatively independent types of valences that can be classified as affective or cognitive, and positive or negative. Affective valences are expectations about feelings while doing an activity; cognitive valences are expectations about the value of the consequences of an activity. In current theories these types of valences are designated as intrinsic, respectively extrinsic motives. Valences, furthermore, can be positive, but also negative. Positive valences give rise to approach motivation, negative valences to avoidance motivation. Important factors that influence valences are autonomy, feasibility expectation, and relatedness, each of which can be distinguished in a personal and a contextual facet, and subjective norm. In conclusion, some theoretical and practical implications are suggested and some issues for future research are proposed.

The focus of this study is the role of the special services coordinator in Dutch primary schools, whose function is to act as a consultant for colleagues regarding students with special needs, and to coordinate the delivery of special services in the school. The question is how the new role is interpreted in primary schools, and whether this interpretation will provoke counterproductive effects. This question is answered by means of an exploratory study in 12 primary schools. The study consists of a survey and interviews with special service coordinators, principals and teachers of Grade 3. Findings suggest that the interpretation of this new role promotes the development of a separated system of special education within the regular school. The delivery of services for students with special needs remains the exclusive task of specialists, and classroom teacher’s learning is not promoted. To promote inclusive education the professional aspects of the special service coordinator’s role as a consultant should be strengthened, and the middle management aspects of the role should be kept in the background.

The aim of this study was to investigate whether polymeric biomaterials can be designed such that they become suitable for surgical closure of medium-sized perforations in the cornea, the transparent tissue in the front of the eye. Such a biomaterial must meet stringent requirements in terms of hydrophilicity, strength, transparency, flexibility, and biocompatibility. Four different copolymers of n-butyl methacrylate (BMA) and hexa(ethylene glycol) methacrylate (HEGMA) were prepared and characterized. Poly(BMA) was made as a reference material. Physicochemical properties were measured (contact angles, glass-transition temperatures, thermal degradation, water uptake and swelling), and cytotoxicity in vitro was assessed with a MTT test. Moreover, the interaction between the materials and cultured human corneal epithelial cells was studied. The copolymers may be useful for temporary closure of corneal perforations.

Purpose . The fitting of toric soft contact lenses is often complicated by interference between the toric optics and the geometry need to stabilise the lens on the eye. The use of a spherical trial lens to determine the parameters of a toric soft contact lens can lead to unintended positioning and movement of the lens ordered. The purpose of this study was to evaluate clinically the success Purpose . The fitting of toric soft contact lenses is often complicated by interference between the toric optics and the geometry needed Method . The design of the lenses used was such that optical correction and stabilisation were separated. The lenses had a back tonic surface limited to the central optical zone and base down prism stabilisation in the periphery. The empirical system used corneal radii, spectacle refraction and horizontal visible iris diameter as lens design parameters. Results . This multi-centre trial, comprised of 105 patients (193 eyes), revealed an overall success rate of 86%. The total number of lenses ordered to achieve success was 1.46 per eye in new patients and 1.69 per eye in patients who were failures with other toric soft lenses. In 14% of the cases success could not be achieved despite ordering several lenses (up to 4 lenses/eye). Many of these patients (60%) were also failures with other toric soft lenses. Conclusion . It is concluded that in new patients successful toric soft contact lens fitting can be achieved with an empirically based method. When refitting former toric soft lens failures, we recommend discontinuation after two further unsuccessful fittings.

( R )-Carvone is a suitable chiral template for the synthesis of differently protected (4 S ,6 R ,7 R )-trihydroxy-1-octyne derivatives, the C 27 C 34 fragment of bryostatins. Also other potentially interesting chiral building blocks are described.

In recent research on school improvement and effectiveness attention is paid to teachers' sense of efficacy. This research is focused on (a) teachers and (b) instructional tasks. Another restriction is that teachers' sense of efficacy is studied apart from the context in which it affects teacher behavior. This study introduces the Teachers' and Principals' Sense of Efficacy scale in pupil and school oriented tasks. The aim of this study is to demonstrate the context dependency of teachers' and principals' sense of efficacy. The central question is to what extent type of task and a staff member's position in the school organization are related to perceived self-efficacy. Besides, teachers' and principals' perceived school efficacy is introduced as a context specific construct. In addition mediating effects of gender, work experience, and grade are analyzed. From the results it is concluded that the expansion of the sense of efficacy construct to principals as well as to school oriented tasks enhances its explanatory potential.

Disconnection at C20-C21 leads to two fragments. The C21-C27 fragment is constructed from D-isobutyl lactate via chelation-controlled allylation. The C17-C20 fragment is obtained from D-pantolactone.

Item does not contain fulltext BACKGROUND/AIMS: Evaluation of the reproducibility of the Lenstar LS 900 non-contact biometer, and a comparison with the Visante anterior-segment optical coherence tomography (AS-OCT) and the IOLMaster. METHODS: Central corneal thickness (CCT), anterior chamber depth (ACD), lens thickness (LT), keratometry (K) values, corneal diameter (CD) and axial length (AL) were obtained in 38 healthy volunteers (76 eyes) to determine the reproducibility of the Lenstar. CCT, ACD, CD, K values and AL measurements measured with the Lenstar were compared with the AS-OCT and IOLMaster. Intraocular lens (IOL) power calculations were done to study the significance of the difference between AL measurements. RESULTS: The reproducibility of the Lenstar was better than 0.9% for CCT, ACD, LT, K values and AL measurements. Although all correlations were highly significant (p

In this study, we assessed the feasibility of a specific elaboration of the efficacy construct, distinguishing between personal and contextual aspects, as a criterion for comparing learning environments. The participants were 163 students from two student-regulated and two teacher-regulated programs in higher education. We measured students’ perceptions of autonomy and various aspects of perceptions of efficacy in common learning tasks. Using principal components analyses, we assessed the structure of all the relevant variables. Subsequently, analyses of variance were performed with regulation source, discipline and grade level as factors. All variables emerged as separate scales with high internal consistency. Students in student-regulated programs reported a higher level of organisational efficacy expectancy, implying that these students perceived better organisational conditions for supporting their task performance. It is concluded that the distinction between personal and contextual aspects of efficacy is a promising distinction. However, a more fine-grained conceptualisation of teacher and student regulation is needed.

The fragments C 1 -C 9 19 and C 11 -C 16 26 of the bryostatins are constructed in an enantioselective and highly diastereoselective fashion from respectively D-pantolactone ( 2 ) and L-erythrulose ( 3 ) as chiral templates.

We investigated the value of newly developed systems for parameter selection on the performance of high Dk rigid gas permeable (RGP) contact lenses with a spheric-aspheric design made of Boston Equa material in normal daily wear conditions. A comparison was also made between the safety and efficacy of a traditional care system vs a one-step chemical care system during the follow-up period of 1 year.A total of 66 patients were randomly assigned to traditional and newly developed systems for computing the back optical zone radius (BOZR) and the total diameter (TD) of the lenses. Evaluation parameters incorporated assessment of fit, visual acuity, wearing time, comfort, and lens condition.The traditional method of computing the BOZR, using a method based on flat-K, predicted the BOZR successfully in 83% of the cases. Corneal topometry reached a lower, but not significantly different (P0.01) value of 75% correct prediction of BOZR. Analysis of the differences in eccentricity (E) values between quadrants per eye was a significant (P0.001) factor in fault predictions in the topometric system. A newly developed guide forTD selection performed, with 90% correct predictions, significantly (P0.01) better than a traditional method (72%) based on corneal diameter on supraversion. No significant differences (P0.05) were found in the capabilities of care systems (a traditional care system using a surfactant cleaner vs a one-step solution) to keep the lenses in proper condition and without deformation, over the 1 year follow-up period. The final success rate was 85%.Although high Dk RGP contact lenses can be fit and used with a 85% success rate using advanced systems for determining the BOZR and TD, it remains necessary to evaluate the fit before dispensing high Dk RGP lenses in 15% of the cases. The one-step solution used in this study was a good starting point for lens care. If needed, surfactant cleaning in the traditional care system can be done without the risk of lens deformation.

This study investigates the effects of subject and track level on the definitions of knowledge used by teachers in secondary education. Responding to 20 scales of an inventory, 202 teachers provided 313 judgments of the characteristics of their own subject as they actually taught it to students of one or more track levels. The first dimension of a principal components solution was interpreted as a contrast between everyday knowledge and academic knowledge. The second dimension involved a contrast between general and specialized knowledge. As far as individual teachers responded to more than one track level, they, generally speaking, maintained a single definition of their subject for all track levels. Subject identity explained most of the differences, but teacher variables were also relevant. If it is allowed to order teachers hierarchically, based on their teacher training and their experience with track levels, then in the group of teachers with the highest level of teacher education and teaching at the highest track level, only the science subjects were judged as extremely hard a n d specialized. In groups of teachers ranking lower, some other subjects such as the foreign languages were judged as relatively hard and specialized, whereas the science subjects were judged less hard and less specialized. The theoretical and practical implications of these findings are discussed.

The aim of this study is to analyze teacher isolation at the level of communication behavior of teachers. The usefulness of communication network analysis is explored in eight elementary schools. The first research question is whether and in what way the communication behavior of teachers varies within as well as between schools. The second research question is how teachers’ communication network participation is related to their perception of different types of tasks. Our findings support the idea that teacher isolation at least partly results from the behavior of individual teachers. Results regarding the relationship between communication network participation and task perception yield insights that can be helpful in developing and supporting collegial relationships in schools.

PURPOSE The aim of this research was to develop a corneal topographer that determines the shape of the entire anterior surface of an eye without assumptions, and with uniformly high accuracy in the center and periphery. METHODS Based upon a double projection of two sine wave gratings and analysis of the distortion of the sine wave gratings due to the corneal-scleral shape, point-by-point measurements of surface elevation were obtained with a sample density equal to the pixel density of the CCD-detector. Using this principle, a prototype topographer, called the Maastricht Shape Topographer (MST), was developed. The accuracy and reproducibility of the instrument were evaluated using bispheric models of the anterior surface of the eye. RESULTS The average accuracy of height measurements was +/- 0.55 micron in the 10-mm central area and +/- 22.50 microns in the periphery (14 to 19 mm). Reconstruction accuracy of the radius of curvature was +/- 0.0155 mm (+/- 0.88 D) in the center and +/- 0.0313 mm in the periphery (sclera). Average height reproducibility standard error was 0.0282 micron in the center and 2.6156 microns in the periphery. CONCLUSIONS With the MST, unambiguous shape measurements of the entire anterior surface of the eye are possible, with accuracy up to clinically accepted standards. MST is able to measure height over a wide area of 20 mm, with a 6-mm depth of field. The tested prototype of the device can be further improved by the use of custom-made optics in order to increase signal to noise ratio in the periphery of the image. This height topographer could offer a reliable method in cases where shape is of paramount importance, e.g., in (scleral) contact lens fitting and refractive surgery.

The influence of pupil size, lens centration, and translation on multifocal contact lens performance suggests that these parameters should be accounted for in the optical design of presbyopic contact lenses. The purpose of the present article is to complete the existing experimental data with clinical measurements of pupil diameter and lens position relative to the pupil in a group of presbyopes, with controlled target luminance, stimulus distance, gaze angle, and convergence. The experiments involve an infrared video-pupillometer and ring-marked contact lenses. Results on pupil aperture show that the effect of changing target distance is comparable in magnitude to that of varying luminance within the photopic range. The measured data on lens position confirm that soft contact lenses are generally decentered from the pupillary axis, usually in inferior temporal direction, and that their average translation between primary and downward gaze is very small. It is also found that the average relative position between lens and pupil centers is slightly modified by changes of luminance in far vision. All these results provide characteristic values which are helpful for the optical modelling of presbyopic contact lenses.

The bryostatins are a novel family of emerging cancer chemotherapeutic candidates isolated from marine bryozoa on the basis of their significant activity against murine P388 lymphocytic leukemia.1 These macrolactones have been shown to exhibit remarkable and unique activities,2 leading to the recent entry of bryostatin 1 (Figure 1) into Phase II clinical trials for the treatment of melanoma, non-Hodgkins lymphoma, and renal cancer.3 While their molecular mode of action is not known, the bryostatins potently inhibit the binding of the tumor-promoting phorbol esters to protein kinase C (PKC) and stimulate enzymatic activity both in vitro and in vivo.4 However, they induce only a subset of phorbol ester responses and block those actions of phorbol esters which they themselves do not initiate, most notably tumor promotion.5 Efforts to identify the structural basis for these and related activities and to develop more effective clinical candidates have been hampered by the low natural abundance1b of the bryostatins and difficulties associated with their modification. As an alternative approach to these goals, we describe here the first class of simplified, synthetic bryostatin analogues which exhibit a high affinity for PKC and potent growth inhibitory activity against several human cancer cell lines. Computational studies,6 limited structure-activity data,1b,6,7 and analogy to diacylglycerol, the endogenous activator of PKC, suggest that the binding of bryostatin to PKC could be attributed to substituents at C1, C19, and C26 (boxed in Figure 1), whose orientations are remotely controlled by a lipophilic spacer (shaded in Figure 1). Macrocycles of the general structure 1 were designed to test this hypothesis. These systems retain the putative recognition domain of the bryostatins but incorporate a simplified spacer domain to facilitate their synthesis. This design allows access to 1 through a novel, convergent esterification-macrotransacetalization strategy involving coupling of the recognition domain (2) with variable spacers (3), an approach which has potential for the creation of analogue libraries. Our first objective in this study was the synthesis of the bryostatin C-ring and its attendant functionality (C15-C27).8 Scheme 1 depicts a first-generation sequence which has readily

Disconnection at C20-C21 leads to two fragments. The C21-C27 fragment is constructed from D-isobutyl lactate via chelation-controlled allylation. The C17-C20 fragment is obtained from D-pantolactone.

The malignant C3H/3T3 mouse cells MO4 invaded embryonic chick heart fragments in an organotypic coculture system on semisolid medium, which mimicked malignant invasion. In this system, at a dose of 1 microgram/ml, the microtubule inhibitors colchicine, demecolcine, vincristine sulfate, vinblastine sulfate, or methyl[5-(2-thienylcarbonyl)-1H-benzimidazol-1-yl]-carbamate (Nocodazole) totally inhibited malignant invasion. At the same dose the drugs were also mitostatic, which was apparent from C-mitoses and from the absence of postmetaphase figures. At a mitostatic dose of 10 microgram/ml, 5-fluorouracil (FUra), cytosine arabinoside, or bleomycin did not interfere with malignant invasion. Combined treatment of the cocultures with the antimetabolite FUra (10 microgram/ml) plus the microtubule inhibitor Nocodazole (1 microgram/ml) completely inhibited invasion. These cocultures also showed the effective inhibition of mitosis by FUra, because Nocodazole-induced C-mitoses were absent. The reversibility of the anti-invasive effect of 4-day treatment with Nocodazole (1 microgram/ml) was demonstrated in shaker cocultures with the use of fluid medium. Our in vitro experiments indicated that cytoplasmic microtubules were involved in malignant invasion and that cell division and invasion constituted separate characteristics of malignant cells.

Ultrastructural investigations on mammalian cells cultured in vitro show that R 17934, a new synthetic anticancer drug, interferes with the structure and function of microtubules, both in interphase and mitotic cells. The activity of this compound in a wide range of experimental tumor systems can thus be explained partly as a direct antimitotic effect and partly as the disintegration of the normal subcellular organization of the nondividing cells. Preliminary investigations in experimental animals show that malignant cells are more susceptible to the antimicrotubular effect of R 17934 than are the nonmalignant cells of the host.