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Biomedical subjects

A Roesch

Publications and source records attributed to A Roesch.

At least 19 recordsLinked to original sources
PubMed2005

Cloning and characterization of the human FCRL2 gene.

We report cloning and characterization of FCRL2, a novel human gene that belongs to the FcR family. The gene is closely linked and structurally similar to the recently identified FCRL/FREB/FcRX gene. The encoded protein is composed of three Ig-like domains and a C-terminal mucin-like domain containing a conserved alpha-helical motif with dileucine signals. Intraexonic splicing may generate two alternative transcripts, coding for isoforms with the third and fourth domains replaced by entirely different amino acid sequences. Like FCRL, the full-length isoform of FCRL2 is expressed intracellularly in transfected 293T cells. Expression analysis revealed FCRL2 mRNA only in placenta. The gene transcripts were not detected in lymphoid tissues or in the main leukocyte subsets isolated from peripheral blood. However, we found that FCRL2 is differentially expressed by transformed B cell lines. Of interest is also the finding that the gene expression may be up-regulated in the progression of melanocytic tumors.

Alternative Splicing↗
PubMed2003

[The dysplastic nevus. Separate entity, melanoma precursor or diagnostic dilemma?].

Today, 20 years after Clark and Elder postulated their tumor progression model of melanocytic lesions from common nevi to melanoma, there are still controversies surrounding this subject. Despite modem molecular biological developments, a consensus about the question, if the dysplastic nevus should be considered as a separate entity, melanoma precursor or just represent a diagnostic dilemma, still seems to be impossible. In addition, since the term melanocytic dysplasia is not precisely defined with regard to all diagnostic methods (clinical morphology, dermatoscopy, dermatopathology, molecular biology), there is considerable confusion. The question remains if a quite arbitrary classification of melanocytic lesions such as dysplastic nevus is useful at all. In daily practice, dermatologists should be aware of the fact that each suspicious melanocytic lesion could represent an early malignant neoplasia, regardless whether it is formally named dysplastic nevus or initial malignant melanoma. We conclude that solid dermatological experience plus novel tools of documentation represent the key factor to minimize patients' risk.

Adult↗
PubMed2003

Computer assisted learning in medicine: a long-term evaluation of the 'Practical Training Programme Dermatology 2000'.

In recent years, numerous computer assisted learning (CAL) programmes based on new teaching methods, as for example the principles of cognitive apprenticeship and problem based learning, have euphorically been developed for various medical fields. However, many of these programmes failed due to either low acceptance, economic inefficiency, or, most seriously, problems with the implementation and evaluation in medical curricula. In 1999, the practical training course 'Dermatology 2000', an interactive multimedia programme for dermatological education, was developed and completely integrated into the regular dermatological curriculum of five German medical schools. The formative evaluation of an implemented relational database revealed contemporary information about the programme's quantity of use. So far, 3050 students have participated in 6557 lessons. The evaluation of two online questionnaires showed a high learner acceptance regarding the programme's instructional design, ergonomics, and didactical presentation and, after completion of Dermatology 2000, an increased interest in medical education software. A comparison of the objective learning outcome illustrated that Dermatology 2000 students (n = 31) not only outperformed non-participants (n = 7) but also showed a (10%) lower rate of errors in a conventional knowledge test. Additionally, single-case studies demonstrated the increased ability of participating students to apply the acquired knowledge to diagnostic problems. We conclude that the implementation of CAL in present medical curricula can contribute to reformations of medical education. The instructional design of Dermatology 2000 is well accepted and suitable to provide both theoretic biomedical knowledge and clinical skills.

Computer-Assisted Instruction↗
PubMed1991

Picumast dihydrochloride (Auteral), a new anti-allergic inhibitor of mediator release and action.

Picumast dihydrochloride (PDH), (3,4-dimethyl-7-[4-chlorobenzyl) piperazine-1-yl]propoxycoumarin dihydrochloride) is a prophylactically active anti-allergic compound which combines inhibition of mediator release and action. The activity profile of PDH differs clearly from that of known prophylactic anti-allergic drugs such as DSCG and ketotifen. Other inhibitory actions of PDH in addition to its H1-antagonism (and that of its metabolites M2 and M1) may be the cause of the suppression of immediate and late phase allergic reactions in animals as well as allergic rhinitis and bronchial responsiveness and symptom scores in asthmatic patients.

Anaphylaxis↗
PubMed1990

Targeting treatment.

As the gathering crisis in health care--its quality, its distribution, and above all its cost--nears the top of the national agenda, hospitals are developing more sharply focused physical responses to a changing spectrum of social and economic forces.

Economic Competition↗
PubMed1989

Influence of picumast dihydrochloride on the ex vivo histamine release from leucocytes of allergic asthmatic patients.

In a pilot study 8 patients with allergic obstructive airway disease were treated with the new compound picumast dihydrochloride (3,4-dimethyl-7-[4-(4-chlorobenzyl)piperazine-1-yl]propoxycoumarine++ + dihydrochloride) 2 x 2 mg daily orally during a period of 8 days additionally to a usual therapy of bronchodilators and corticoids in a steady state. It was demonstrated that the compound inhibited the allergen induced histamine liberation of patients basophils significantly. Compared with a collective of patients without an additional picumast dihydrochloride treatment the effect of the substance was shown more clearly. From reasons of these experimental data picumast dihydrochloride may be of a considerable value as a prophylactic agent in allergic bronchial asthma when given orally.

Asthma↗
PubMed1989

Antiallergic activity of picumast dihydrochloride in several animal species.

Picumast dihydrochloride (3,4-dimethyl-7-[4-(4-chlorobenzyl)piperazine-1-yl]propoxycoumarin dihydrochloride) was compared with cromoglycate, ketotifen and mepyramine as an inhibitor of allergic and anaphylactoid reactions. 1. In guinea-pigs, pretreatment with picumast dihydrochloride given intravenously, orally or by inhalation prevented bronchospasm induced by antigen or histamine. The fraction of the bronchospasm remaining after mepyramine pretreatment was further reduced by picumast dihydrochloride. 2. Systemic administration of picumast dihydrochloride inhibited antigen-induced conjunctivitis, whereas mepyramine and ketotifen were inactive. 3. Intravenous and oral pretreatment with picumast dihydrochloride inhibited the antigen-induced mast cell degranulation in rat mesentery. The effective doses of cromoglycate given intravenously were twice as high as those of picumast dihydrochloride. Picumast dihydrochloride did not inhibit antigen-induced bronchoconstriction in rats. 4. The cutaneous reaction induced with Ascaris antigen in atopic monkeys was insensitive to the antihistaminic action of ketotifen, whereas it was inhibited by low doses of picumast dihydrochloride. Both compounds suppressed skin reactions induced by histamine. 5. Picumast dihydrochloride decreased IgE production in atopic high responder mice. It did not prevent autoimmune nephritis in NZB/W mice. 6. In rats, picumast dihydrochloride did not reduce cotton pellet granuloma, nor adjuvant arthritis. The inhibition of carrageenin oedema is presumably due to its anti-oedematous properties rather than to an antiproliferative activity. In conclusion, the inhibition of allergic and anaphylactoid reactions by picumast dihydrochloride can be attributed to a combined inhibition of liberation and action of histamine and other mediators.

Airway Resistance↗
PubMed1989

Metabolism of picumast after administration of picumast dihydrochloride and antiallergic activity of the main metabolites.

The present experiments were carried out to elucidate the chemical structure and the pharmacological activity of the main metabolites of picumast (3,4-dimethyl-7-[4-(4-chlorobenzyl)piperazine-1-yl]propoxycoumarin ). The metabolic pathways were identical in animals and man, but there were major quantitative differences. The fraction of the radioactivity in the plasma attributable to the parent compound 0.5 to 3 h after oral administration of picumast dihydrochloride was less than 15% in animals but 95% to 57% in man. Inhibition of the C3-zymosan-induced chemilumiescence of human leucocytes was taken as an indicator of the diminished liberation of mediators and inhibition of the histamine-induced contraction of isolated guinea-pig lung strips as an example for the antagonism of picumast dihydrochloride to mediators of allergic reactions. Stepwise oxidation of the 3-methyl substituent of the coumarin ring to the alcohol and the carbonic acid increased the histaminolytic potency, but decreased the inhibition of chemiluminescence. Another metabolite formed by cleavage of the piperazine-containing side chain was inactive in both tests.

Animals↗
PubMed1989

Pharmacokinetics of picumast after administration of 14C-picumast dihydrochloride in dogs, rats, rabbits and monkeys.

In dogs, rats, monkeys and rabbits, picumast (3,4-dimethyl-7-[4-(4-chlorobenzyl)piperazine-1-yl]propoxycoumarin ) is eliminated from the plasma by metabolic clearance. Its main metabolic pathway is oxidation of the 3-methyl group of the coumarin ring. After oral administration, the parent compound accounted for less than 15% of the concentration of radioactivity in the plasma. In rats the hydroxylation product M2 was the main metabolite in the plasma; in the other species it was the carbonic acid M1. The hydroxylation of picumast was highly saturable, whereas further oxidation was independent of the dose in dogs and only slightly dose-dependent in rats. Picumast, M1 and M2 are pharmacologically active and potentially toxic. The sum of all three was defined as active compounds. The renal clearance of the active compounds, particularly of picumast, was very low. The terminal half-lives of the active compounds varied between 11 h in rats and 26 h in monkeys. The low plasma concentrations of other metabolites are at least partly due to their renal clearance. In dogs the bioavailability of the parent compound was 14%, the absorption of radioactivity 68%. Of radioactivity injected intravenously 54.8% was recovered from the faeces, 21.8% from the urine. The minimum toxic plasma concentrations of the active compounds were calculated from the minimum toxic dose (MTD) found in chronic or reproduction toxicity studies and the ratio Cl/f of total body clearance/bioavailability determined in the present investigations. The results showed that the differences between the MTDs in dogs and rats and on administration in rats by gavage or in the diet are largely due to differences in total body clearance and bioavailability.

Absorption↗
PubMed1985

Quantitative evaluation of ototoxic side effects of furosemide, piretanide, bumetanide, azosemide and ozolinone in the cat--a new approach to the problem of ototoxicity.

A new method for the quantitative assessment of acute ototoxic side effects of drugs is described. It is suitable for screening purposes. The method is based on the determination of the toxic dose (TD50) which causes a defined hearing loss in 50% of the animals tested. The hearing loss is defined as a complete suppression of the compound action potential (CAP) of the auditory nerve, elicited by clicks 30 dB above threshold. This is approximately equivalent to a clinical hearing loss of 30 dB. The TD50 is used to estimate the therapeutic range. With this approach ototoxic side effects of furosemide, piretanide and bumetanide were compared quantitatively in cats. The TD50 values for CAP suppression were 18.37 mg/kg for furosemide; 4.29 mg/kg for piretanide and 2.21 mg/kg for bumetanide. As equipotent diuretic doses are 2.61 mg/kg for furosemide, 0.26 mg/kg for piretanide and 1.16 mg/kg for bumetanide, it appears that the relative ototoxicity is least for piretanide and highest for bumetanide. Plasma concentrations, determined initially and when recovery of CAP to 50% of control had occurred, indicate that bumetanide may be more slowly eliminated from the cochlear spaces than furosemide and piretanide. In addition azosemide and ozolinone were tested. The TD50 for azosemide was less than 10 mg/kg. With ozolinone where there are two isomers, only the diuretic (-)ozolinone was ototoxic; the TD50 was less than 100 mg/kg.(ABSTRACT TRUNCATED AT 250 WORDS)

Action Potentials↗
PubMed1978

[Bronchial asthma due to occupation allergy of immediate type (I) to platinum salts (author's transl)].

Occupational inhalation allergy (bronchial asthma, rhinitis, conjunctivitis), often in association with urticaria and Quincke oedema is common in platinum associated industry. It is due to sensitization against platinum chloride. The reaction mechanism corresponds to the immediate type (I) allergy as shown by clinical tests (skin tests), in virtro (histamine release from leucocytes) and in vivo investigations (passive cutaneous anaphylaxis in apes). The degree of sensitization is so high that test investigations in affected persons must be performed with care. For prick testing with platinum chloride (PtCl6)2- or (PtCl4)2- an initial concentration of 10(-9) g/ml is recommended. As an average of 60% of people working in the platinum industry fall ill with bronchial asthma more stringent protective occupational measures are suggested.

Angioedema↗