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Biomedical subjects

H de Vries

Publications and source records attributed to H de Vries.

At least 19 recordsLinked to original sources

The use of adrenocorticotrophic hormone (4-9) analog ORG 2766 in autistic children: effects on the organization of behavior.

In a double-blind placebo-controlled crossover trial, 14 autistic children were treated with the neuropeptide ORG 2766, a synthetic analog of adrenocorticotrophic hormone (ACTH) (4-9). ORG 2766 treatment (20 mg per day during 4 weeks) was associated with an increased amount and an improved quality of the social interaction of the autistic children with a familiar experimenter. These changes in interaction were clinically relevant. Following treatment with ORG 2766 gaze and smile behaviors of child and experimenter showed stronger temporal contingencies. Further, after ORG 2766, stereotypies were temporally disconnected from verbal initiatives. The data supported the notion of a stimulating effect of ORG 2766 on social interaction. The implications of these findings for the endogenous opioid theory of autism are discussed.

Adrenocorticotropic Hormone

Deficits in social behavior in autism and their modification by a synthetic adrenocorticotrophic hormone (4-9) analog.

When charting the structure of the social behavior of autistic children by means of an ethologically analyzed playroom session, deficits appeared in the reciprocity of eye-contact and in the location of verbal initiatives. These deficits in social behavior were beneficially influenced by treatment with the adrenocorticotrophic hormone (4-9) analog ORG 2766.

Adrenocorticotropic Hormone

Increased sensitivity of an adriamycin-resistant human small cell lung carcinoma cell line to mitochondrial inhibitors.

The energy metabolism of an atypical multidrug resistant human small cell lung carcinoma cell line (GLC4/ADR) was studied. The glycolytic rate was 30% reduced and the glucose-6-phosphate dehydrogenase activity 2-fold increased in GLC4/ADR compared to the parental sensitive line (GLC4). Although mitochondrial respiration activities were similar in both cell lines, GLC4/ADR was more sensitive to the antimitochondrial drugs doxycycline and oligomycin, while cross-resistance was observed for the glycolytic inhibitor 2-deoxyglucose and for the antimitochondrial drug rhodamine-123. Continuous incubation with doxycycline induced a dramatic reduction of mitochondrial mRNAs in both cell lines, whereas a strong reduction of the nuclear-coded mRNA for subunit IV of cytochrome c oxidase was induced in GLC4/ADR only. Incubation with doxycycline had an additive effect on the cytotoxicity of adriamycin in both cell lines. Thus, a form of collateral sensitivity to antimitochondrial drugs may exist in atypical multidrug resistant cell lines.

Adenosine Triphosphate

Photoactivation of 2-nitrofluorene in vitro and in the rat in vivo. UVA-induced formation of reactive intermediates that bind covalently to RNA and protein.

2-Nitrofluorene (2-NF), an environmental pollutant, can be activated by UV light to reactive intermediates that bind covalently to RNA and protein in vitro: high levels of covalent binding were obtained. This covalent binding was not dependent on the presence of oxygen in the solution and could be decreased by glutathione. Hydrolysis of the in vitro modified RNA and subsequent analysis of the liberated bases by HPLC revealed that approximately 15% of the covalent binding of 2-NF to RNA could be attributed to the formation of a guanosine adduct of nitroreduced 2-NF, N-(deoxyguanosin-8-yl)-2-aminofluorene. Many other adducts are formed of which the structure and mechanism of formation are as yet unknown. The possibility of photoactivation of 2-NF in the rat in vivo was also investigated. Photoactivation increased covalent binding of 2-NF in the skin but not in other organs. The mechanism of the photoactivation of 2-NF is discussed.

Animals

The adrenocorticotrophic hormone (4-9) analog ORG 2766 benefits autistic children: report on a second controlled clinical trial.

In a second controlled crossover trial, 20 autistic children received 40 mg/day of the neuropeptide ORG 2766, a synthetic analog of ACTH (4-9), for 8 weeks. Parents' checklist ratings (ABC) as well as clinicians' ratings (CGI) pointed to significant improvements after the course of treatment; improvements were clearest on the ABC social withdrawal subscale. The analysis of individual target symptoms and the parents' treatment preferences substantiated the beneficial effects of ORG 2766. In an ethologically analyzed playroom session, ORG 2766 treatment was associated with an improvement in the children's play behavior and a significant increase in the social interaction between child and experimenter. Gaze coordination between child and experimenter also was improved.

Adolescent

The utilization of qualitative and quantitative data for health education program planning, implementation, and evaluation: a spiral approach.

The process of development of a Dutch smoking prevention project is described. An essential feature of the project is the combination and interaction of qualitative and quantitative research methods. It is advocated that each method has its own contribution and can be considered as a separate methodology contributing to social science in general and health education research in particular. Combining the two approaches in a spiral approach will result in a synergistic effect, because of the interaction of both approaches. The results of both methods suggest that qualitative methods enhanced the generation of ideas and theories. Qualitative methods were used to formulate ideas for improving quantitative data gathering, analyzing and comparing ideas with respect to program development, and for testing the internal validity of a quantitative design. The quantitative method enabled testing of results in different groups and detecting detailed differences. It also provided information that one of the assumptions of the program, the development of a teacher independent program, was not completely realized. The major advantage of using both methods is that this provides feedback between assumptions and data, thus enhancing comparison of results and critical reflection during the whole project.

Health Education

[Paced addition. A neuropsychological test for assessment of divided attention].

The Pasat (Paced auditory serial addition task) is a test requiring addition of simple digits presented auditorily in several series of a successively higher pace of presentation. The task reflects the capacity for divided attention, is a measure of information processing speed and has appeared to be sensitive to minor attention deficits. We made a Dutch version characterized by longer time intervals between digits, for use in a study among (altogether 130) middle-aged and elderly persons. This modified version was evaluated with respect to feasibility. It appeared to be fairly feasible, provided sufficient opportunity for practice is given. Two series with inter-stimulus intervals of 4 and 3 seconds respectively were then evaluated with respect to validity and reliability in subjects of 48 to 74 years. Both Pasat series correlated well with two tests of attention: Digit Symbol (WAIS) and d2-test (r = 0.53-0.67), the relation with reaction decision speed being generally weak (r = 0.29-0.33) and weak to absent with a number of memory tests (r = -0.04-0.29). The Pasat performance shows a positive relationship with educational level and intelligence (inter-stimulus interval 4 seconds: r = 0.28 and 0.33 resp.; inter-stimulus interval 3 seconds: r = 0.40, 0.57 resp.). The stability of test performance over a period of about two months is moderate (r = 0.54, 0.61 resp.). In view of the excellent inter-observer reliability (r = 0.99) and the good parallel-test reliability (r = 0.79, 0.68 resp.), this might be explained by fluctuations in the capacity measured, rather than measurement error.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged

Identification of three human pseudogenes for subunit VIb of cytochrome c oxidase: a molecular record of gene evolution.

Three pseudogenes for the nuclear-encoded subunit VIb of cytochrome c oxidase (COX) were isolated by screening a human genomic library with cloned human cDNA coding for COX subunit VIb. The nucleotide sequences of the pseudogenes, designated psi COX6b-1, psi COX6b-2 and psi COX6b-3, were determined. Pseudogene psi COX6b-1 bears all the hallmarks of a processed pseudogene and diverged from the parental gene after the divergence of man and cow. Alu repetitive elements were integrated into the structural sequences of the other two pseudogenes. Comparison with the human and bovine cDNA sequences encoding COX subunit VIb suggests that psi COX6b-2 and psi COX6b-3 were formed earlier in evolution than psi COX6b-1. Genomic Southern analysis indicated that a few more pseudogenes for COX subunit VIb are likely to be present in the human genome. Identical nt differences with respect to the human cDNA sequence in the pseudogenes provide some clues on the evolution of the ancestral gene coding for COX subunit VIb.

Amino Acid Sequence

Comparative toxicity of organotin compounds to rainbow trout (Oncorhynchus mykiss) yolk sac fry.

The comparative toxicity of various organotin compounds was investigated in early life stages of the rainbow trout. Beginning with yolk sac fry, trout were continuously exposed for 110 days to tributyl- (TBTC), triphenyl- (TPhTC) or tricyclohexyltin chloride (TCHTC) at concentrations of 0.12-15 nM, to trimethyltin chloride (TMTC) at concentrations of 3-75 nM or to dibutyl- (DBTC) or diphenyltin chloride (DPhTC) at 160-4000 nM. The diorganotin compounds DBTC and DPhTC were about three orders of magnitude less toxic than the triorganotin homologs TBTC and TPhTC. Both for DBTC and DPhTC, a no-observable-effect concentration (NOEC) of 160 nM was established, corresponding to 40 and 60 ppb, respectively. Of the triorganotin compounds, TCHTC appeared to be the most toxic, inducing 100% mortality within 1 week at a concentration of 3 nM. Only a few trout survived exposure to 0.6 nM TCHTC for 110 days. TBTC and TPhTC caused acute mortality at a concentration of 15 nM. For both TBTC and TPhTC a NOEC of 0.12 nM was established, corresponding to water concentrations of 40 and 50 ppt, respectively. Histopathological examination revealed depletion of glycogen in liver cells of both di- and triorganotin exposed fish, except in the case of TMTC. No signs of toxicity were observed in fish exposed to up to 75 nM TMTC, the highest concentration tested. Atrophy of the thymus, the most prominent sign of toxicity of di- and tributyltin compounds in mammalian species, was not observed in early life stages of rainbow trout. Tail melanization was observed in the groups exposed to 3 nM TPhTC, 3 nM TBTC, 800 nM DBTC and 800 nM DPhTC. At the end of the exposure period, resistance to infection was examined by an intraperitoneal challenge with Aeromonas hydrophila, a secondary pathogenic bacterium to fish. Resistance of bacterial challenge was found to be decreased even at the lowest-effect concentration of both di- and triorganotin compounds.

Aeromonas

[Chronic thromboembolic cor pulmonale in pacemaker-associated right atrial thrombi. Pulmonary thromboendarterectomy with removal of the electrodes as a life-saving measure].

Life-threatening chronic cor pulmonale occurred in a 22-year-old woman with congenital 3 degrees atrioventricular block, 6 years after implantation of a pacemaker and 3 1/2 years after removal of the pacemaker (the electrodes were too firmly attached to be removed). The emboli originated from the right-atrial thrombi which had formed around the electrodes left in situ. The embolic source shrank during systemic administration of urokinase, initially 600,000 IU in 60 min, then 100,000 IU per hour, and pulmonary perfusion improved transiently. Nonetheless the patient became breathless on the slightest physical exertion. Recurrent syncopal attacks with marked increase of pulmonary artery pressure necessitated pulmonary thrombendarterectomy and removal of the electrode and wires. Thereupon the patient's condition clearly improved so that 6 months postoperatively her exercise tolerance was again unimpaired.

Adult

Assignment of the gene coding for human cytochrome c oxidase subunit VIb to chromosome 19, band q13.1, by fluorescence in situ hybridisation.

A cloned, 40 kb, genomic DNA fragment, containing the last exon of the gene for human cytochrome c oxidase subunit VIb and its flanking sequences, was used as a probe to localize the subunit VIb gene on human metaphase chromosomes. The probe was labelled with Bio-11-dUTP and detected by fluorescence. Subsequent R-banding indicated that the cytochrome c oxidase subunit VIb gene is localized in band 19q13.1, extending the evidence that the human nuclear genes of cytochrome c oxidase are not clustered.

Biotin

Differences in the structure of social behaviour of autistic children and non-autistic retarded controls.

Social and task-oriented behaviours of autistic children were compared to those of individually age- and IQ-matched non-autistic retarded controls. Autistic children showed deficits in visual reciprocity, in indicating joint attention and referential head gestures, and in the integration of gaze and gestures when reacting to tasks. The findings confirmed the notion of social and pragmatic communicative deficits in autism. The implications of these findings for theories of social behaviour in autism (avoidance, facial perception, theory of mind) are discussed.

Autistic Disorder

Severe reductions in transcripts for cytochrome c oxidase during erythropoiesis in vitro do not lead to inactive mitochondria in reticulocytes.

At some stage during erythroid cell differentiation proliferation of the cell stops and its organelles are removed and degraded. We wanted to know how mitochondrial function correlated with the synthesis of products necessary for functional mitochondria. We studied the time course of the presence of a nuclear and a mitochondrial transcript for the mitochondrial enzyme cytochrome c oxidase as well as that of the enzyme activity itself in differentiating murine splenic erythroid progenitors (erythroid colony-forming units, CFU-E) in vitro. Whereas the amount of total RNA as well as the transcripts for subunits II and IV of cytochrome c oxidase (COX II and COX IV) per cell decreased to low levels, the amount of globin mRNA increased from zero in CFU-E (t = 0) to high levels in late erythroblasts (21 h). Thus, RNA synthesis as such was not inhibited. The cytochrome c oxidase activity also declined. In the total culture, total RNA as well as the mRNAs for COX II and IV decreased after 7 h. The enzyme activity increased until 21 h and decreased after that. The early decrease of the transcripts, followed after a lag phase of 14 h by a decrease in enzyme activity, ultimately does not result in inactive mitochondria in the reticulocyte stage, as was shown with a mitochondria-specific fluorescent probe.

Animals

Isolation of cDNAs encoding subunit VIb of cytochrome c oxidase and steady-state levels of coxVIb mRNA in different tissues.

A full-length cDNA clone specifying the nuclear-encoded subunit VIb of human cytochrome c oxidase (COX) was isolated from a human skeletal muscle cDNA expression library. This was done with antiserum directed against the group of subunits VIa, b and c of bovine heart COX. A potential ribosome-binding site was located immediately upstream from the initiation codon. The predicted amino acid sequence revealed 85% similarity with the corresponding subunit of bovine heart COX. Subunit VIb lacks a cleavable presequence for mitochondrial addressing. We assume that there are no tissue-specific isoforms of subunit VIb, since (i) in a Northern blot experiment a single hybridizing band of approx. 500 nucleotides was demonstrated in RNA from liver, skeletal muscle, MOLT-4 cells and fibroblasts and (ii) a full-length cDNA clone with an identical sequence was isolated from a human liver cDNA library. Steady-state levels of the coxVIb transcript were different in the tissues examined.

Base Sequence

Photochemical reactions of quindoxin, olaquindox, carbadox and cyadox with protein, indicating photoallergic properties.

Quindoxin (quinoxaline-1,4-dioxide), a former 'growth promoter' used in animal husbandry, has been taken from the market because of its photoallergic properties. Nowadays its derivatives olaquindox, carbadox and cyadox are frequently applied for the same purpose. Recent reports show that olaquindox too, can induce photoallergic skin reactions in stockmen. From the present investigation it appeared that all compounds mentioned, form a reactive oxaziridine upon exposure to light, just like many other imino-N-oxides. Photoreactivity with protein, which is considered as an important condition for a compound to be a potential photoallergen, was also studied. Quindoxin and olaquindox proved to meet this condition, as was expected. But carbadox and cyadox also react and were shown to be even more reactive towards human serum albumin.

Animals

Phototoxicity of olaquindox in the rat.

Because of its photoallergic properties quindoxin, a growth promoting feed additive used for example in cattle raising, has been taken off the market. Recently, it appeared that the quindoxin derived olaquindox (OLAQ), used for the same purpose, also produces these light-induced side effects. In this study, phototoxicity of OLAQ was investigated by comparing four groups of rats with a different daily regime: 1 = light plus OLAQ, 2 = dark plus OLAQ, 3 = light (no OLAQ), 4 = dark (no OLAQ). It appeared that rats of group 2 excreted per day approximately 60 per cent of their daily dose as OLAQ and approximately 2 per cent as OLAQ-4-monoxide, whereas these figures were approximately 19 per cent and 30 per cent, respectively, for the light-exposed animals. Besides, rats of group 1 only, suffered from severe erythema, oedema and necrosis of the ears after four days treatment. It is probable that OLAQ, photoactivated in the skin, forms a reactive oxaziridine, analogous to what has been found with the tranquilliser chlordiazepoxide (Librium; Hoffmann La Roche), another imino-N-oxide.

Animals