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Biomedical subjects

W Bender

Publications and source records attributed to W Bender.

At least 73 records · Page 4Linked to original sources
PubMed1990

Assessment of compliance-related attitudes in psychiatry. A comparison of two questionnaires based on the Health Belief Model.

In a study of 118 psychiatric patients two questionnaires of similar content that are supposed to predict compliance with pharmacotherapy in psychiatry were examined, "COSS" and "KK-Skala". These questionnaires assess the patient's attitudes towards his illness, pharmacotherapy, and the physician. Patient compliance was judged by the treating physicians. The results of discriminant analyses indicated that about two thirds of the patients were correctly classified into "compliant" and "moderately or not compliant" (as judged by the physicians) by means of COSS and KK-Skala, respectively. It is a matter for further research whether these results reflect in fact moderate associations between patient attitudes and compliant behavior or are due to limitations of the questionnaires and of the study design.

Adult↗
PubMed1990

Base and sequence specificities of aflatoxin B1 binding to single- and double-stranded DNAs.

The inhibitory effect of alfatoxin B1 (AFB1) on the template function for RNA synthesis of several single- and double-stranded DNAs with known base content and sequence was studied in vitro. The results showed that AFB1 strongly inhibits the template function of poly[d(G-C)] and has little, if any, effect on poly[d(A-T)]. Using [3H]AFB1 for the binding, and by spectrum analysis of the appearance of a broad AFB1-DNA adduct peak between 300 and 400 nm right after the typical DNA peak at 260 nm, it is possible to conclude that the binding preference of AFB1 to DNA is: poly[d(G-C)] greater than polydG.polydC greater than polydG greater than polydC, with no detectable binding to poly[d(A-T)]. These studies have therefore provided evidence that the selective inhibition of DNA template function is a direct reflection of the binding specificities of AFB1 to DNA. Furthermore, since there is a 3-fold binding preference of AFB1 for poly[d(G-C)] over polydG.polydC on an equal weight basis, and with very low binding affinity toward either G or C when it is in single-stranded form, these data also suggest: (i) AFB1 binds preferentially to DNA with an alternating G-C sequence compared to DNA with a sequence of contiguous Gs or Cs; and (ii) intercalation may be part of the mechanism for the binding of AFB1 to DNA.

Aflatoxin B1↗
PubMed1990

abdA expression in Drosophila embryos.

The abdominal A (abdA) gene is one of three transcription units in the Bithorax Complex of Drosophila encoding a homeo box protein; it is flanked by Ultrabithorax (Ubx) and Abdominal B (AbdB). The abdA gene is required for segmental identity of the second through eighth abdominal segments. The transcription unit of abdA is approximately 20 kb long and encodes a protein of 330 amino acids. The abdA homeo box is almost identical to the homeo box of Ubx but is quite different from the AbdB homeo box. A polyclonal antibody to abdA protein stains embryonic nuclei in segments A1-A7 (parasegments 7-13). The iab-2, 3, and 4 mutant classes define positive cis-regulatory elements that induce expression of abdA in segments A2-A4 (parasegments 7-9), respectively. Once a pattern of abdA expression is turned on in a given parasegment, it remains on in the more posterior parasegments, so that the complex pattern of expression is built up in the successive parasegments. The abdA product appears to repress expression of Ubx whenever they appear in the same cell, but abdA is repressed by AbdB only in the eighth and ninth abdominal segments.

Amino Acid Sequence↗
PubMed1990

Actinomycin D binding in vitro: active chromatin preferred.

When [3H] Actinomycin D (Act. D) is used to interact with nuclei and nucleoli in vitro, it binds preferentially to nucleolar chromatin. The preferential binding is no longer detectable, when purified nuclear and nucleolar DNAs are used. In parallel, Act. D preferentially inhibits nucleolar over nuclear RNA synthesis when chromatin templates are used, and the preferential inhibition is lost when purified nuclear and nucleolar DNAs are used. It is concluded: 1) the preferential inhibition of nucleolar over nuclear RNA synthesis by Act. D is a direct reflection of the preferential binding of Act. D to the nucleolar chromatin; and 2) the nucleolar chromosomal proteins, not the nucleolar DNA, confer the preferential binding of Act. D.

Animals↗
PubMed1989

Construction of large DNA segments in Escherichia coli.

Recombinant DNA clones containing large pieces of DNA are useful in the study of large genetic units, but these are difficult to make in most bacterial cloning vectors. A strategy is described that uses general and site-specific recombination to construct large pieces of eukaryotic DNA from smaller cloned segments. The large clones are propagated on F factor-based plasmids in Escherichia coli. They can be easily modified to introduce mutations or rearrangements. These techniques were applied to the construction of large DNA segments from the bithorax complex of Drosophila.

DNA, Recombinant↗
PubMed1989

Increased potency of antagonists of substance P having asparagine in position 6.

The general structure of antagonists of substance P (SP) which was found with the development of Spantide and analogs based on Spantide served for further refinement. The antagonistic potency was tested in vitro on guinea pig ileum and taenia coli. It was unexpectedly found that introduction of Asn6 gave rise to a considerable increase in potency. The exchange of Gln6 for Asn6 entails the shortening of the side chain by one CH2 unit and seems slight for steric advantages and potency increase. The analog [D-Arg1,D-Cl2Phe5,Asn6,D-Trp7,9,Nle11]SP had pA2 values of 7.4 (ileum) and 8.0 (taenia coli). We then used this sequence as a new lead to introduce new changes, which were made in positions 1, 3, 5, 7 and 9. It was found that Arg1 is important, but Lys3 can be exchanged. The Pal3 derivative had pA2 values of 8.1 and 8.0 and the Nle3 counterpart had 7.7 and 7.4 D-Cl2Phe is an effective substituent in position 5. D-Trp in positions 7 and 9 were superior to other alternatives.

Amino Acid Sequence↗
PubMed1989

Molecular analysis of recombination events in Drosophila.

The locations of crossover junctions and gene conversion tracts, isolated in the rosy gene of Drosophila melanogaster, were determined using DNA sequencing and denaturing gradient gel electrophoresis. Frequent DNA sequence polymorphisms between the parental genes served as unselected genetic markers. All conversion tracts were continuous, and half of the reciprocal crossover events had conversion tracts at the crossover junction. These experiments have also identified the sequence polymorphisms responsible for altered gene expression in two naturally occurring rosy variants.

Animals↗
PubMed1989

Safety and efficacy of roxatidine acetate. Evidence from pharmacodynamic and clinical trials.

The effects of a new H2-receptor antagonist, roxatidine acetate, have been investigated in both clinical and pharmacodynamic trials in Europe and the United States. A series of four double-blind randomized studies are reviewed, reporting the effects of different dose regimens of roxatidine acetate compared with ranitidine and placebo in healthy volunteers using continuous intragastric pH monitoring. These pharmacodynamic studies clearly demonstrate that roxatidine acetate is an effective gastric antisecretory agent, which is up to twice as potent as ranitidine. The results of several clinical studies of roxatidine acetate in patients with gastric as well as duodenal ulcer conducted in Europe, Japan, and the United States are also reviewed. These studies show that roxatidine acetate is comparable to other potent H2-receptor antagonists in terms of cumulative healing rates, pain relief, and safety. Overall, the pharmacodynamic and clinical data indicate that the efficacy of roxatidine acetate 75 mg twice-daily (b.i.d.) does not differ significantly from ranitidine 150 mg b.i.d. Roxatidine acetate is equally effective in the treatment of peptic disease including gastric ulcer, duodenal ulcer, and reflux esophagitis.

Cimetidine↗
PubMed1989

[Full inpatient versus partial inpatient psychiatric after-care--a comparative retrospective study].

In a retrospective study 80 inpatients (Sociotherapy, Therapeutic Community) were compared to 160 outpatients (80 patient Day Clinic, 80 patients Night Clinic). With a mean treatment duration of 4-5 1/2 month a significant decrease was found for each group in the frequency and duration of further hospital admissions after end of therapy. Day and Night Clinic patients tending to a better outcome than the inpatients. Advantages of the Day and Night Clinic are seen e.g. in a higher degree of acceptance by patients and family doctors, disadvantages in the increased rate of suicide found in our sample.

Adult↗
PubMed1989

Pharmacokinetic characteristics of roxatidine.

This article reviews the published and unpublished results of pharmacokinetic studies with roxatidine acetate in healthy volunteers of different ethnic origins, patients with various degrees of renal impairment, patients on maintenance hemodialysis, lactating women, and elderly patients. In addition, it reports on the findings of interaction studies with food and other drugs. The pharmacokinetic characteristics of roxatidine were found to be nearly identical for different doses, formulations, and ethnic groups. The decrease in relative total clearance (oral clearance) in patients with renal impairment and in the elderly can be explained almost completely by their level of renal function. As expected from the pharmacokinetic characteristics in healthy volunteers, only a small amount of roxatidine is removed by hemodialysis. Dose reduction is recommended in patients with renal impairment, but dose supplementation after hemodialysis is not necessary. Only a negligible fraction of the dose administered is excreted with breast milk. No pharmacokinetic interactions were found with theophylline, warfarin, propranolol, diazepam, and desmethyldiazepam, antipyrine or antacids. Food did not interfere with the absorption or disposition of roxatidine.

Aged↗
PubMed1989

[Inpatient rehabilitation of chronic schizophrenic patients with a behavior therapy token reinforcement program].

The efficacy of a token economy system was assessed in a study involving 76 chronic schizophrenics who were inpatients during a treatment period of four years. The interrelations between therapeutic success on the one hand, and socio-economic as well as course of disease-related factors on the other were studied, including psychopathology and the efficacy of token economy.

Adult↗
PubMed1988

Alternative RNA products from the Ultrabithorax domain of the bithorax complex.

The homeotic gene, Ultrabithorax (Ubx) is involved in specifying the identities of several segments in the fly Drosophila melanogaster. The structures of over 60 independent Ubx cDNAs have been examined. There are two major species of transcripts, 3.2 and 4.3 kb in length, which are produced by alternate sites of polyadenylation. Differential splicing gives rise to at least five variant Ubx proteins. The variant forms share common 5' and 3' exons but differ in their small internal 'micro' exons. Additional variation is generated by two separate splice donor sites at the end of the common 5' exon, situated 27 bp apart. Northern hybridization and S1 nuclease protection studies of RNA from various developmental stages and tissue types reveal that the alternate splicing and the choice of polyadenylation site are each differentially regulated in both a temporal and a tissue specific manner. Additional transcripts were found just downstream of the Ubx transcription unit, which may be products of the lethal left of bithorax gene (llb).

Animals↗
PubMed1988

Sequences of the gypsy transposon of Drosophila necessary for its effects on adjacent genes.

The Drosophila melanogaster transposon gypsy is the cause of numerous spontaneous mutations, most of which are suppressible by mutations in the suppressor of Hairy wing [su(Hw)] locus. We have examined the phenotype of four revertants of the gypsy element-induced mutation bithoraxoid1 (bxd1) and determined the molecular basis of these reversions. All four revertants have undergone deletions within the gypsy element. The altered gypsy element from one of the partial revertants has been cloned. It has a deletion of only 109 base pairs near the 5' end of the gypsy transcription unit. Similar deletion gypsy elements exist elsewhere in the Drosophila genome. We discuss a mechanism by which the 109-base segment might affect the bxd phenotype.

Animals↗
PubMed1988

Correlation studies between the binding of aflatoxin B1 to chromatin components and the inhibition of RNA synthesis.

Aflatoxin B1 (AFB1) is a potent inhibitor of rat liver nuclear and nucleolar RNA synthesis. However, since after activation AFB1 binds to both DNA and chromosomal proteins, the question is which form of binding is responsible for the inhibition of RNA synthesis. Male Sprague-Dawley rats (200 g) were given i.p. injections of 10, 50, 100, 300 and 500 micrograms AFB1 per 100 g body wt containing 50 microCi [3H]AFB1 (sp. act. 25 Ci/mmol), and the animals sacrificed 2 h later. Liver nuclei, nucleoli and P-3 (a transcriptionally active subnucleolar fraction that is 3.4-fold enriched in active rDNA) were isolated and the binding of AFB1 to DNA and protein of each fraction was determined by DNase I digestion and 5% trichloracetic acid (TCA) hydrolysis. We found that the binding of AFB1 to both nuclear and nucleolar DNA plateaus at 300 micrograms AFB1 per 100 g body wt with values around 100 and 400 pmol AFB1 per mg nuclear and nucleolar DNA, respectively. On the other hand, the binding to protein is linear, although with different slopes, for both nuclear and nucleolar fractions even at 500 micrograms AFB1 per 100 g body wt, the highest dose used. Since AFB1 inhibition of nuclear and nucleolar RNA synthesis plateaus respectively at 60% and 90% inhibition levels at the dose of 300 micrograms AFB1 per 100 g body wt, these results suggest the binding of AFB1 to DNA, but not to protein, is responsible for the inhibition of RNA synthesis. Further support for this contention is obtained by comparing the binding and the inhibition data between P-3 and nucleoli. P-3 is three times more transcriptionally active than nucleoli and, as a result, is more sensitive to AFB1 inhibition. This greater sensitivity is reflected by the specific binding activity of AFB1 to P-3 DNA, which is greater than 50% higher than to nucleolar DNA. In contrast, this effect is not reflected by the specific binding activity of AFB1 to protein which is exactly the same for both fractions.

Aflatoxin B1↗
PubMed1988

The binding of aflatoxin B1 to rat liver nuclear proteins and its effect on DNA-dependent RNA synthesis.

This paper reports studies on the binding of aflatoxin B1 (AFB1) to rat liver nuclear proteins in vivo and in vitro, and its effect on RNA synthesis. Two hours after rats (200 g) were given a single i.p. injection of 300 micrograms AFB1 containing 50 microCi [3H]AFB1/100 g body wt, AFB1 was found bound to the free nuclear proteins (29.7 pmol/mg protein), histones (20.3 pmol/mg protein) and chromatin-bound non-histone proteins (13.8 pmol/mg protein). The binding of AFB1 to histones was further studied in vitro. We found that for a given type of histone, the binding level varied greatly depending on the conditions used. Under both in vivo and in vitro conditions, however, H3 was always the most efficient substrate, and H4/H2B always the least efficient substrates for AFB1 binding. These results suggest that the binding preference was mainly related to the intrinsic properties of the histone type, and was little affected by the geometric arrangement of the histones in chromatin. Using nuclear proteins added to the RNA synthesizing system in vitro, we found that only the histone fraction had a strong inhibitory effect. Further studies, however, indicated that this inhibition was not due to histones per se, but rather to poly-ADP-ribosylated histones present in the histone preparations. No detectable difference in effect was found between control and AFB1-bound nuclear proteins on RNA synthesis. Moreover, higher levels of AFB1 binding to histones did not potentiate the inhibitory effect. We therefore conclude, and in direct support to our previous correlation studies (see the preceding paper), that the binding of AFB1 to nuclear proteins has no inhibitory effect on RNA synthesis.

Aflatoxin B1↗
PubMed1988

Clinical characteristics of roxatidine acetate: a review.

Pharmacodynamic studies revealed that 150 mg of roxatidine acetate were optimal in suppressing gastric acid secretion, and that a single bedtime dose of 150 mg was more effective than a dose of 75 mg twice daily in terms of inhibiting nocturnal acid secretion. When administered orally as a capsule containing a granule formulation, the drug displayed modified-release properties, which led to a sustained suppression of gastric acid secretion. Clinical trials revealed that roxatidine acetate, 75 mg twice daily and 150 mg at night, was highly effective in healing duodenal and gastric ulcers and in reducing ulcer pain, over 4, 6, and 8 weeks of therapy. A steady reduction in diameter was observed in those ulcers not completely healed during therapy. The single bedtime dose regimen, while producing the same degree of healing as the divided daily dose during controlled clinical trials, may be of greater value in therapeutic use owing to improved patient compliance. In all efficacy criteria (cure, reduction in ulcer size, and pain relief) there was no significant difference between roxatidine acetate in a total daily dose of 150 mg, ranitidine in a total daily dose of 300 mg, and cimetidine in a total daily dose of 800 mg. Prevention of gastric and duodenal ulcer relapse was achieved by roxatidine acetate, 75 mg at night for 6 months, in about 70% of patients, as determined in open, pilot studies--a rate comparable to those reported for cimetidine and ranitidine. Roxatidine acetate shares with ranitidine an improved safety profile when compared with cimetidine. Human pharmacology studies and short-term and long-term clinical trials have all shown that roxatidine acetate is an exceptionally well tolerated compound, without the antiandrogenic activity and interference with hepatic drug metabolism which have characterized cimetidine treatment. A reason for the improved safety profile of roxatidine acetate may be its greater potency than cimetidine (six times less potent) and ranitidine (half as potent), so that lower doses of roxatidine acetate, representing a lower chemical load, are therapeutically effective. The novel structure of roxatidine acetate probably also underlies the improved safety of the compound.

Cimetidine↗
PubMed1987

Mutations affecting expression of the rosy locus in Drosophila melanogaster.

The rosy locus in Drosophila melanogaster codes for the enzyme xanthine dehydrogenase (XDH). Previous studies defined a "control element" near the 5' end of the gene, where variant sites affected the amount of rosy mRNA and protein produced. We have determined the DNA sequence of this region from both genomic and cDNA clones, and from the ry+10 underproducer strain. This variant strain had many sequence differences, so that the site of the regulatory change could not be fixed. A mutagenesis was also undertaken to isolate new regulatory mutations. We induced 376 new mutations with 1-ethyl-1-nitrosourea (ENU) and screened them to isolate those that reduced the amount of XDH protein produced, but did not change the properties of the enzyme. Genetic mapping was used to find mutations located near the 5' end of the gene. DNA from each of seven mutants was cloned and sequenced through the 5' region. Mutant base changes were identified in all seven; they appear to affect splicing and translation of the rosy mRNA. In a related study (T. P. Keith et al. 1987), the genomic and cDNA sequences are extended through the 3' end of the gene; the combined sequences define the processing pattern of the rosy transcript and predict the amino acid sequence of XDH.

Animals↗