PubMed Health⌕ Search

Biomedical subjects

W Bender

Publications and source records attributed to W Bender.

At least 55 records · Page 3Linked to original sources
PubMed1994

Studies on the binding and transcriptional properties of aflatoxin B1-8,9-epoxide.

[3H]Aflatoxin B1-8,9-epoxide ([3H]AFB1-8,9-epoxide), the putative ultimate carcinogen of AFB1, was synthesized and tested for its binding specificity to and transcriptional effect on several single- and double-stranded DNAs containing cytosine. The test was carried out over a 200-fold concentration range (i.e. 0.1-20 microgram [3H]AFB1-8,9-epoxide per 0.025 A260 units of DNA). The results show: (i) [3H]AFB1-8,9-epoxide bound preferentially to the double-stranded alternating co-polymer poly[d(G-C)] over the double-stranded poly(dG).poly(dC) and single-stranded poly(dG) or poly(dC) homopolymers. (ii) The binding affinity of [3H]AFB1-8,9-epoxide to poly(dC) was essentially the same as the poly(dG). (iii) Under identical conditions, [3H]AFB1-8,9-epoxide bound to poly(dG).poly(dC) 2.5-3 times more than to poly[d(I-C)]; however, poly[d(I-C)]-directed RNA synthesis was clearly more sensitive to [3H]AFB1-8,9-epoxide inhibition than poly(dG).poly(dC). Conversely, the binding affinity of [3H]AFB1-8,9-epoxide to poly(dC) and to poly[d(I-C)] was quite similar, yet poly(dC)-directed RNA synthesis was much more resistant to [3H]AFB1-8,9-epoxide inhibition than poly[d(I-C)]. (iv) After [3H]AFB1-8,9-epoxide was hydrolyzed to [3H]AFB1-8,9-dihydrodiol (0.01 N NaOH, 10 min 23 degrees C), it was no longer able to bind poly[d(G-C)] or to inhibit poly[d(G-C)]-directed RNA synthesis. These results confirm our earlier studies using microsome-activated AFB1 and AFB1-Cl2 that AFB1 after activation is able to bind cytosine in DNA, and the binding is not via AFB1-8,9-dihydrodiol. Furthermore, the results also suggest that AFB1 adducts may not have the same biological effect depending on the base, sequence as well as the conformation of the DNA where the adducts are formed.

Aflatoxin B1↗
PubMed1994

Enhancer traps in the Drosophila bithorax complex mark parasegmental domains.

Eight P elements carrying a beta-galactosidase (lacZ) reporter have been mapped to sites within the Drosophila bithorax complex. The bithorax complex contains three homeotic genes, and at least nine regulatory regions which control their expression in successive parasegments of the fly. The enhancer traps inserted at the promoter of one of the genes, Ultrabithorax, express lacZ in patterns which mimic the Ultrabithorax protein pattern. Enhancer traps in the regulatory regions do not mimic the endogenous genes, but express lacZ globally in the relevant parasegments. Some P elements carry large DNA fragments upstream of the lacZ promoter but internal to the P element. In cases where these internal sequences specify a lacZ pattern, that pattern is generally suppressed when the element is inserted in the bithorax complex. In embryos mutant for genes of the Polycomb group, the lacZ expression from the enhancer traps spreads to all segments. Thus, the enhancer traps reveal parasegmental domains that are maintained by Polycomb-mediated repression. Such domains may be realized by parasegmental differences in chromatin structure.

Animals↗
PubMed1993

Elements of the Drosophila bithorax complex that mediate repression by Polycomb group products.

The Polycomb (Pc) group genes encode repressors that restrict expression of homeotic genes to precise domains along the anterior-posterior (A-P) axis. We describe germ-line transformation constructs, containing portions of the bxd, iab-2, or iab-3 regulatory regions of the bithorax complex (BX-C), that are controlled by Pc group products in embryos. There are multiple BX-C elements that mediate Pc group control, which we call Pc group response elements (PREs), and they can work when removed from the normal BX-C context. These constructs are each regulated by the genes Polycomb (Pc), extra sex combs (esc), Enhancer of zeste (E[z]), polyhomeotic (ph), Polycomb-like (Pcl), Sex comb on midleg (Scm), Posterior sex combs (Psc), and Additional sex combs (Asx), consistent with multiple Pc group products acting together. Depending upon context, a PRE from the iab-3 region can restrict expression in different A-P positions. Thus, PREs are not specialized for particular parasegments, suggesting that Pc group products do not directly specify A-P boundaries of homeotic expression. Instead, the results support the idea that Pc group products provide stable memory or imprinting of boundaries which are initially specified by gap and pair-rule regulators.

Animals↗
PubMed1993

Abraham Flexner--a crusader against medical maleducation.

The Flexner Report, one of the most cited publications in medical education, describes the site-visits to 163 medical schools in 40 American states, in terms of admission requirements, number of students, number of faculty, etcetera. The Flexner Reports (there are three!) are still worth reading. For instance, Flexner holds a plea for problem orientation. "The student is to collect and to evaluate facts. The facts are locked up in the patient. To the patient, therefore, he must go." The impossibility of obtaining encyclopaedic knowledge requires medical students to adopt a scientific attitude; this calls for dedicated teachers, not necessarily from the research establishment. Flexner recommended the closing down of 124 medical schools, not only because of the deplorable quality, but also because of the disproportionate geographical distribution, and (most of all) because of the enormous overproduction of medical doctors. Flexner's significance as a medical educator is illustrated by a discussion of the role of the teacher and the nature of medical education. Learning, not teaching, is what it is all about. It is argued that cancer education can learn from Flexner's insights.

Canada↗
PubMed1993

[Epidermal cysts and folliculitis caused by cyclosporin A].

A 66-year-old man was treated with cyclosporin A (Sandimmun) after a kidney transplant and developed numerous epidermal cysts, comedones and folliculitis in the 2nd year of the immunosuppressive therapy. The eruptions were more marked on the back and in the temporal and retroauricular regions of the face. Histological examination of a cystic tumour revealed a follicular cyst of the acro-infundibular type. While hypertrichosis and gingival hyperplasia are now well known as side effects of cyclosporin A, cystic and acneiform skin lesions must also be attributed to this drug.

Acne Vulgaris↗
PubMed1992

Psychomotor disturbances in psychiatric patients as a possible basis for new attempts at differential diagnosis and therapy. V. Evaluation of psychomotor training programs in depressed patients.

Parts I-III of this series used psychometric assessment of motor performance in psychiatric patients and indicated a "psychotic-motor syndrome" (PMS) in schizophrenic and affective psychoses, which was not found in "neurotic"/reactive or healthy persons. Part IV yielded signs of concomitant brain dysfunction in these patients, demonstrated by EEG mapping as well as other (SPECT/PET) neuroimaging methods. Apart from this "basic science" interest into the pathophysiology of endogenous psychoses we engaged in the development of motor training programs using the PMS as "target" syndrome. We hypothesized, that motor training would not only improve disturbed motor behaviour, but ameliorate other symptoms of psychopathology also. These assumptions were supported in the first two independent studies involving n = 45 and n = 31 ICD-9 mono- and/or bipolar endogenous depressed patients, respectively (the studies on schizophrenic patients being reported finally as part VI of this series, along with the final version of our modified motor test battery). Examples of the motor training programs are provided in this paper, although the final version of the complete programs will be published separately for space reasons and for better availability for routine clinical use.

Adult↗
PubMed1992

Ten different Polycomb group genes are required for spatial control of the abdA and AbdB homeotic products.

Mutations in genes of the Polycomb (Pc) group cause abnormal segmental development due to ectopic expression of the homeotic products of the Antennapedia and bithorax complexes. Here the requirements for Pc group genes in controlling the abdA and AbdB products of the bithorax complex are described. Embryos containing mutations in the genes Polycomb (Pc), extra sex combs (esc), Enhancer of zeste [E(z)], polyhomeotic (ph), Sex comb on midleg (Scm), Polycomb-like (Pcl), Sex comb extra (Sce), Additional sex combs (Asx), Posterior sex combs (Psc) and pleiohomeotic (pho) were examined. In every case, both abdA and AbdB are expressed outside of their normal domains along the anterior-posterior (A-P) axis, consistent with these Pc group products acting in a single pathway or molecular complex. The earliest detectable ectopic expression is highest in the parasegments immediately adjacent to the normal expression boundary. Surprisingly, in the most severe Pc group mutants, the earliest ectopic AbdB is distributed in a pair-rule pattern. At all stages, ectopic abdA in the epidermis is highest along the anterior edges of the parasegments, in a pattern that mimics the normal abdA cell-specific pattern. These examples of highly patterned mis-expression show that Pc group mutations do not cause indiscriminate activation of homeotic products. We suggest that the ectopic expression patterns result from factors that normally activate abdA and AbdB only in certain parasegments, but that in Pc group mutants these factors gain access to regulatory DNA in all parasegments.

Animals↗
PubMed1992

[Drug management and therapy resistance. A cross-sectional study of schizophrenic patients in a large psychiatric hospital].

In a cross-sectional study 473 schizophrenic patients of a great psychiatric hospital were served. It was looked for differences in patients' characteristics and pharmacotherapy according to the therapeutic-functional structure of the hospital (admission-Unit, sociotherapeutic and long-time wards). Differences in drug-management became evident on basis of a regimen, which applies high doses (number of psychotropic drugs, chlorpromacin-units) in general, despite recommendations in the literature. The treatment refractory patients in the long-time wards are found to be heterogeneous and the authors suggest alternative pharmacological and psychosocial interventions.

Adult↗
PubMed1991

[The influence of biographical details in case reports on diagnostic judgment].

Diagnostic judgment of medical students is influenced by patients they have seen recently. Not only signs and symptoms but also biographic data of the demonstrated patient contribute to this phenomenon. In this study the question is raised whether practising physicians are susceptible to the same influence after reading a case report in a medical journal. A case to be published in this journal was transformed into two patient scripts. The first was based on the same diagnosis and the same signs and symptoms, the second was based on another diagnosis and contained partly similar partly different signs and symptoms. Both scripts contained the same, striking biographic data derived from the original case report. One of the two scripts was presented randomly to a control group of 53 practising doctors before the date of publication. They were asked to rate the probability of 8 diagnoses on a 7-point scale. The experimental group consisted of 16 doctors who stated having read the case report. The scores of both groups were compared using analysis of variance. The experimental group in both cases assigned a significantly higher probability to the diagnosis of the published case report. In the first case they were right, in the second they were wrong. These results are similar to the findings with medical students. The question to be explored further is how to present patient cases in medical education. On one hand they should be attractive with some real life data, on the other hand spectacular biographic data may impair the diagnostic process.

Demography↗
PubMed1991

Transcriptional effect of aflatoxin B1 on cytosine and/or hypoxanthine containing DNAs.

The effect of aflatoxin B1 (AFB1) on the template function for RNA synthesis of several single and double-stranded synthetic DNAs containing cytosine (C) and/or hypoxanthine (H) bases is studied in vitro. The results indicate that AFB1, after liver microsome activation, strongly inhibits the template function of poly[d(I-C)] and has little, if any, effect on polydI.polydC, polydI, or polydC. This conclusion is reached whether rat liver nuclear free RNA polymerase or E. coli RNA polymerase is used for the transcription. The mechanism of this inhibition is believed mainly due to the inhibition of elongation of RNA synthesis, because autoradiography of the [alpha-32 P]GTP labeled RNAs after polyacrylamide gel electrophoresis clearly shows that the size of the RNA from AFB1 treated group is dramatically reduced. The evidence that the selective inhibition of poly[d(I-C)] template function is a direct reflection of the binding of AFB1 to poly[d(I-C)] is provided by the use of radioactive [3H]AFB1 for the binding and by spectrum analysis of the appearance of a broad AFB1-DNA adduct peak between 300 nm and 400 nm right after the typical DNA peak at 260 nm. These data, which are in direct support to our recent report (F.L. Yu, et al., Carcinogenesis, 11, 475-478, 1990), suggest that the binding of AFB1 prefers alternating, double-stranded DNA, and the binding affinity of AFB1 to DNA is greatly reduced when the bases are in either single- or double-stranded homopolymer forms.(ABSTRACT TRUNCATED AT 250 WORDS)

Aflatoxin B1↗
PubMed1991

Evidence for the covalent binding of aflatoxin B1-dichloride to cytosine in DNA.

In vitro studies of the effect of aflatoxin B1-dichloride (AFB1-Cl2) on the template function for RNA synthesis of several single- and double-stranded synthetic DNAs containing cytosine and/or hypoxanthine bases are reported. The results indicate: (i) AFB1-Cl2 strongly inhibits the template function of the single-stranded homopolymer polydC and has no effect on polydI, (ii) the inhibition is stronger when cytosine is in the double-stranded alternating copolymer poly[d(I-C)], and (iii) polydI directed RNA synthesis can be inhibited if it is in the double-stranded homopolymer polydI.polydC, although the template function of the polydC strand is still inhibited to a greater extent. The evidence that the selective inhibition of the DNA template function is a direct reflection of the binding specificities of AFB1-Cl2 is provided by the binding studies of [3H]AFB1-Cl2 to these DNAs. The binding of AFB1-Cl2 to polydC is substantiated by the dose-response template inhibition and by the dose-response template binding studies. Additionally, these results show that AFB1 per se has neither inhibitory nor binding activity. Auto radiography of [alpha-32P]GTP labeled RNAs suggests that the mechanism of inhibition of polydC template function by AFB1-Cl2 is mainly due to the inhibition of the elongation of RNA synthesis. Spectrum measurement of the products of enzyme digestion of the AFB1-Cl2 modified polydC reveals that the deoxycytidine fraction gives a typical cytosine absorption peak at 275 nm followed by a broad peak between 300 and 400 nm with a maximum at 390 nm. High performance liquid chromatography confirms the existence of a cytosine-AFB1 adduct which absorbs strongly in the regions between 250 and 400 nm with peaks identifiable at 260, 350 and 390 nm. These results strongly suggest that AFB1 in the activated form of AFB1-Cl2 is able to covalently bind to cytosine in DNA.

Aflatoxin B1↗
PubMed1991

Mapping point mutations in the Drosophila rosy locus using denaturing gradient gel blots.

Mutations within the rosy locus of Drosophila were mapped using blots of genomic DNA fragments separated on denaturing gradient gels. DNA sequence differences between otherwise identical small rosy DNA fragments were detected among the mutants as mobility shifts on the blots. Mutations were mapped to within a few hundred base pairs of rosy sequence in 100 of 130 mutants tested--a 77% detection rate. The sequence changes in 43 rosy mutations are presented; all but six of these were single base changes. Thirty-four of 36 sequenced mutations induced by the alkylating agents N-ethyl-N-nitrosourea and ethyl methanesulfonate were transitions. All of the mutations mapped in the rosy transcription unit. Twenty-three of the 43 sequenced mutations change the predicted rosy gene polypeptide sequence; the remainder would interrupt protein translation (17), or disrupt mRNA processing (3).

Animals↗
PubMed1991

Gene conversion in Drosophila and the effects of the meiotic mutants mei-9 and mei-218.

Simple meiotic gene conversion tracts produced in wild-type females were compared with those from two meiotic mutants, mei-9 and mei-218. The positions and lengths of conversion tracts were determined by denaturing gradient gels and DNA sequencing. Conversion tracts in wild type averaged 885 base pairs in length, were continuous, and displayed no obvious hot spots of initiation. Some unusual conversion events were found in the mei-218 and mei-9 samples, although most events were indistinguishable from wild-type tracts in their length and continuity.

Animals↗
PubMed1991

The way we train the clinical eye through slides.

Inspection is an important clinical skill. It is remarkable that in basic medical education this skill is not specially trained. To remedy this, we have developed a method of instruction at Groningen University Hospital to train inspection. We give an outline of the method and provide examples of dialogue.

Clinical Competence↗
PubMed1991

[The effectiveness of therapeutic horseback-riding in the treatment of chronic schizophrenic patients. Experimental results and clinical experiences].

After describing horse-riding as a facility in managing mentally ill patients, a program for chronic schizophrenic in-patients is presented. Clinical experience with this program and also results of a controlled study are reported. The therapeutic value and slope for horse-riding are discussed in relation to different diagnoses.

Adaptation, Psychological↗
PubMed1990

Regulatory elements of the bithorax complex that control expression along the anterior-posterior axis.

The Drosophila bithorax complex (BX-C) controls segmental development by selectively deploying three protein products, Ubx, abd-A and Abd-B, within specific segments along the body axis. Expression of these products within any one segment (or, more accurately, parasegment) is affected by mutations clustered in a particular region of the BX-C. The regulatory regions defined by this genetic analysis span 20-50 kb and there is one region for each segmental unit. Here we describe regulatory elements from several of these regions, identified by fusion to a Ubx-lacZ gene and analysis in germline transformants. A small DNA fragment from the abx region programs expression with an anterior boundary in the second thoracic segment (parasegment 5). This anterior limit is appropriate, since the abx region normally controls Ubx in parasegment 5. Other regulatory regions of the BX-C that control development of parasegments 6, 7 or 8 contain similar regulatory elements that program expression with anterior limits in parasegments 6, 7 or 8, respectively. These experiments define a class of BX-C regulatory elements that control expression along the anterior-posterior axis. The early appearance of the lacZ patterns in embryos suggests a role for these elements in the initial activation of expression from the BX-C.

Animals↗