Biomedical subjects
K Mariën
Publications and source records attributed to K Mariën.
Establishing tolerable dungeness crab (Cancer magister) and razor clam (Siliqua patula) domoic acid contaminant levels.
Domoic acid has been found in razor clams (Siliqua patula) and dungeness crabs (Cancer magister) in Washington State and elsewhere on the West Coast of the United States. Due to toxic effects associated with domoic acid exposure, an effort has been made to establish tolerable domoic acid levels in crabs and clams obtained from commercial harvest and sale and from individual recreational harvesting. To accomplish this, the amount of clams and crabs consumed by populations of concern was determined, a tolerable daily intake (TDI) was developed for individuals most sensitive to effects of this compound, and the TDI was equated with consumption patterns to determine tolerable clam and crab domoic acid levels. Results indicate that the primary health effects associated with domoic acid toxicity can be averted in populations of concern and for others consuming crabs or clams less frequently (or in lesser quantity) if domoic acid contaminant concentration does not exceed 30 mg/kg in the hepatopancreas and viscera of dungeness crabs or 20 mg/kg in clams.
Determination of a tolerable daily intake of DDT for consumers of DDT contaminated fish from the lower Yakima River, Washington.
DDT, DDE, and DDD have been detected at elevated concentrations in sediments and fish of the Yakima River, its tributaries and drainages. An assessment was conducted to evaluate the public health significance of eating fish from the river. This was accomplished by establishing a daily intake level of DDT for the population of greatest concern, and comparing this level to a tolerable daily intake. The most sensitive and highly exposed group was determined to be breastfeeding infants. Infant daily intakes of DDT, based on estimated mother's DDT-breast milk levels, were compared to a recommended tolerable daily intake. Results indicate that mothers who frequently consume Yakima River bottom-feeding fish could have breast milk DDT concentrations sufficiently high to expose their infants to levels above the tolerable daily intake.
Treatment of hyperkeratotic skin diseases with R 68151, a topical 5-lipoxygenase inhibitor: four case reports.
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A patient bothered by unexpected sources of isothiazolinones.
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Replication blocks and sequence interaction specificities in the codon 12 region of the c-Ha-ras proto-oncogene induced by four carcinogens in vitro.
We have examined the region surrounding codon 12 in the human c-Ha-ras proto-oncogene in vitro to determine the reaction intensities at the guanine nucleotides after exposure to the mycotoxin aflatoxin B1, to one of its human metabolites aflatoxin M1, to dimethyl sulfate, and to the major ultimate carcinogen of benzo(a)pyrene, benzo(a)pyrene diol-epoxide. Among the adducts produced, those at N-7-guanyl sites are alkali-labile and can be identified using a variation of the Maxam-Gilbert sequencing procedure. Data indicate that the guanine nucleotides of codon 12 have above average potential for adduct formation by the genotoxins when compared to other guanine sites, but were not the strongest sites. This codon 12 region has been inserted into single-stranded M13 phage, exposed to several of the genotoxins, and used as a template for DNA synthesis in vitro. There is a sequence-specific variation in polymerase inhibition at various adducted nucleotide sites, but replication blocks are not preferentially seen at the carcinogen-adducted guanines of codon 12. These results indicate that the predominance of point mutations which are detected in vivo at codon 12 do not reflect sequence-mediated preferential susceptibility of these sites to initial DNA adduction or to replication errors. The mechanisms controlling these sequence effects are not currently understood, and attempts to predict relative alkylation or termination frequencies based solely on local DNA sequence are not reliable.
Site-specific aflatoxin B1 adduction of sequence-positioned nucleosome core particles.
The question of how the presence of nucleosomal packing of DNA modifies carcinogen interaction at specific sites cannot be answered by studies on whole chromatin or bulk nucleosomes because of the heterogeneity of DNA sequences in the particles. We have circumvented this problem by using nucleosomes that are homogenous in DNA sequence and hence in DNA-histone contact points. A cloned DNA fragment containing a sea urchin 5 S gene which precisely positions a histone octamer was employed. By using 32P end-labeled DNA and genotoxins that allow cleavage at sites of attack, the frequency of adduction at every susceptible nucleotide can be determined on sequencing gels. The small methylating agent dimethyl sulfate and the bulky alkylating agent aflatoxin B1-dichloride (AFB1-Cl2) were used to probe the influence of DNA-histone interactions on DNA alkylation patterns in the sequence-positioned core particle. We find dimethyl sulfate to bind with equal preference to naked or nucleosomal DNA. In contrast, AFB1-Cl2 binding is suppressed an average of 2.4-fold at guanyl sites within nucleosomes compared with AFB1-Cl2 affinity at the corresponding site in naked DNA. The DNA is more accessible in regions near the particle boundary. We observe no other histone-imposed localized changes in AFB1-Cl2 sequence specificity. Further, sites of DNase I cleavage or proposed DNA bending show neither enhanced nor reduced AFB1-Cl2 adduction to N7-guanine. Since AFB1-Cl2 binding sites lie in the major groove, nucleosomal DNA appears accessible to AFB1-Cl2 at all points of analysis but with an access which is uniformly restricted in the central 100 nucleotides of the core particle. The data available do not indicate further localized or site-specific perturbations in DNA interactions with the two carcinogens studied.
Comparative binding and sequence interaction specificities of aflatoxin B1, aflatoxicol, aflatoxin M1, and aflatoxicol M1 with purified DNA.
The covalent binding of the activated forms of several aflatoxins to N-7 of guanine residues on purified DNA has been studied. The aflatoxins include aflatoxin B1 (AFB1) and two human metabolites, aflatoxicol and aflatoxin M1, along with aflatoxicol M1, a rabbit and trout metabolite. DNA binding studies using tritiated [3H]aflatoxins indicate that equimolar solutions of each aflatoxin upon activation with chloroperoxybenzoic acid readily react to produce covalently bound adducts. These reactions produce alkali-labile sites which can be identified using a simple variation of the Maxam-Gilbert sequencing procedure. Two DNA fragments were exposed to each aflatoxin, and the reaction intensities at 33 guanine residues were determined. As much as 10-fold variation in reaction intensities was observed for various guanyl sites. Data indicate that none of the aflatoxins had identical reaction profiles, although AFB1 and aflatoxicol M1 were similar, as were aflatoxicol and aflatoxin M1. Hence, the frequency with which the various aflatoxin epoxides might damage specific sites critical for tumor initiation in vivo would not be predictable from total covalent binding indices. The frequency of occurrence of modifications at particular sites for AFB1 was also compared with the empirical "rules" established for AFB1 by Misra et al. (Misra, R. P., Muench, K. F., and Humayun, M. Z. (1983) Biochemistry 22, 3351-3359). Identical sites within fragments were compared for each aflatoxin, and the data showed that the attacking frequency for some such sites varied significantly. These results indicate that binding intensity rules based on nearest neighbor nucleotides do not reliably predict guanyl-AFB1 binding frequencies.
Adult linear IgA bullous dermatosis with bronchial involvement.
A 54-year-old man is described, suffering from adult linear IgA bullous dermatosis with involvement of the bronchial mucosa. The main respiratory symptoms were recurring haemoptysis, episodic narrowing of the airways and persistent non-specific bronchial hyperreactivity. On CT scan the trachea had a saber-sheath shape with tracheal ring calcification. Endoscopically the tracheo-bronchial mucosa was diffusely purpuric and hyperaemic and also showed pale elevated plaques, bullous lesions and ulceration. Histological examination of biopsies of skin and nasal and tracheo-bronchial mucosa showed subepithelial blister formation associated with an accumulation of polymorphonuclear cells at the epithelial-subepithelial junction, and linear IgA deposits on direct immunofluorescence.
Connubial dermatitis from a hair lotion.
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Experience with itraconazole in treatment of fungal infections.
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Occupational fixed eruption by inhalation of pyrazolones.
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A passive diffusion 222Rn sampler based on activated carbon adsorption.
A simple passive sampler for 222Rn with up to 24-hr integration times can be constructed by using a diffusion barrier to regulate the effective sampling rate of an ambient temperature activated carbon bed. The diffusion element serves to make sampler performance relatively independent of the properties of the type of carbon used. Satisfactory results are obtained if the total effective sample volume is kept well below the equivalent air volume of the activated carbon bed. The influence of various temperature and Rn profiles on the sampler's performance have been examined by experiment and by simulation. The amount of Rn adsorbed may be measured by gamma spectroscopy, by outgassing into an alpha scintillation flask, or by desorption into a liquid scintillator. In the latter case, a sensitivity of 0.2 pCi l-1 is obtainable for 24-hr exposures.
Itraconazole in the treatment of dermatophytoses: a comparison of two daily dosages.
Itraconazole, the first orally active triazole antifungal agent, was tested in 185 cases of acute or chronic (recurrent) dermatophytosis. The skin infections were divided into two major diagnostic groups: tinea corporis/tinea cruris (91 cases) and tinea pedis/tinea manuum (94 cases). Each patient was randomly assigned to a regimen of 50 or 100 mg of itraconazole daily. Of the cases of tinea corporis and/or tinea cruris, 94% responded to 50 mg of itraconazole daily and 96% to 100 mg daily. The effects of therapy were evident earlier when 100 mg daily was given. Of the cases of tinea pedis and/or tinea manuum, 80% responded to 50 mg of itraconazole daily and 94% to 100 mg. Again, improvement was seen sooner with the 100-mg regimen. Only five patients (2.9%) reported minor adverse reactions. Hematologic and blood-biochemical parameters were monitored before treatment and at biweekly intervals thereafter in 37 patients; no significant abnormalities were observed. Thus, either 50 or 100 mg of itraconazole daily constitutes effective treatment for dermatophytoses. Since the larger dosage induces a faster response, it should be evaluated further.