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J Schmid

Publications and source records attributed to J Schmid.

At least 163 records · Page 9Linked to original sources
PubMed1987

In vivo screening of glutathione related detoxification products in the early state of drug development.

Glutathione (GSH) adducts and consecutive degradation products thereof are indications of reactive intermediates during drug metabolism. As demonstrated with the analgesic SX-PP 16 (4-amino-3,5-dibromacetanilide), however, interactions of a drug with GSH can be detected by labelling the GSH-stores with labelled cysteine, and consecutive administration of the unlabelled drug even at therapeutic doses. The GSH-adducts are sensitively and specifically traced by HPLC, applying column-switching and a combination of diode-array- and radioactivity detection. This approach seems to be much more sensitive than a classical GSH-depletion study. The structure of the main metabolite of SX-PP 16 (46% of urinary excretion) was elucidated as 3-bromo-4-amino-5-mercapturyl-acetanilid.

Acetanilides↗
PubMed1986

[Carcinoma in mature cystic teratoma of the ovary: pathology, therapeutic and prognostic problems].

Carcinoma develops in about 1-2% of ovarian mature cystic teratomas, usually in postmenopausal women, squamous cell carcinoma being the most common tumor type. This study is based on a review of 300 published and 5 new cases. The carcinomatous tissue tends to invade adjacent organs, whereas lymph node metastasis has rarely been diagnosed. A five-year survival rate of about 15% testifies to the poor prognosis. The treatment of tumors confined to the ovary (stage Ia, Ib; FIGO) usually consists of bilateral oophorectomy and total hysterectomy. Exceptionally, in young women of childbearing age, treatment may be limited to unilateral oophorectomy. A thorough surgical, cytologic and bioptic examination of the abdominal cavity should be done to confirm an early tumor stage. In more advanced stages (FIGO Ic to IV), complete eradication of the malignant tissue offers the only chance of cure. The efficacy of chemo- and radiotherapy has not been studied systematically. We suggest that carcinoma in mature cystic teratoma be staged and treated according to the guidelines established for common epithelial neoplasms of the ovary.

Adenocarcinoma↗
PubMed1986

Synthesis and antineoplastic activity of CNC-cysteamine and related compounds.

N'-[N-(2-Chloroethyl)-N-nitroso]carbamoyl cysteamine (CNC-cysteamine) and several related compounds have been synthesized and tested against L 1210 leukemia in mice. Reaction of N-(2-chloroethyl)-N-nitrosocarbamoyl azide (CNC-azide) with cysteamine yielded CNC-cysteamine and bis(CNC)cystamine. Reaction of CNC-azide with cystamine in the presence of triethylamine gave bis(CNC)cystamine. Unexpectedly, formation of CNC-cystamine carboxylazide as a minor reaction product was also observed. N-(2-Chloroethyl)carbamoyl cysteamine 2-chloroethylcarbamate was formed when 2-chloroethyl isocyanate was reacted with cysteamine. Nitrosation of this cysteamine N,S-dicarbamoyl derivative led to formation of a mixture of two dinitroso isomers. Preliminary testing of the newly synthesized CNC-derivatives against L 1210 leukemia in mice revealed that CNC-cysteamine, its disulfide bis(CNC)cystamine and CNC-cystamine carboxylazide were highly active against L 1210 leukemia.

Animals↗
PubMed1986

[Supracondylar upper arm fracture in childhood].

For the last 28 years condylar upper arm fractures have been treated at the Department of Surgery of Erlangen University mainly via the extention after Baumann. 182 cases out of 306 were followed up clinically. Extension treatment after Baumann is a technically simple procedure and offers the possibility of continual control and correction of repositioning. Treatment results are good. We could not observe Volkmann's contraction among our patients. Operation does not decisively improve the results, whereas the risk is increased. It should remain restricted to those cases only which cannot be successfully treated by conservative measures.

Casts, Surgical↗
PubMed1985

Structural relationship of human interferon alpha genes and pseudogenes.

We have isolated and characterized DNA segments containing IFN-alpha-related sequences from human lambda and cosmid clone banks. We describe six linkage groups comprising 18 distinct IFN-alpha-related loci, and report the nucleotide sequences of nine chromosomal IFN-alpha-genes with intact reading frames, as well as of five pseudogenes. Taking into account as yet unsequenced genes as well as clones described by others, there are now seven linkage groups and 23 loci, of which 15 correspond to potentially functional genes and six to non-functional genes; two loci remain unsequenced. Eighteen additional sequences are likely to be allelic to the above. The finding that at least two IFN-alpha genes appear to be natural hybrids of other IFN-alpha genes, and that two distinct IFN-alpha loci have completely identical coding sequences, although their flanking regions are different, is evidence for information exchange between the individual genes.

Amino Acid Sequence↗
PubMed1984

Clinical pharmacology of oral psoralen drugs.

Proper oral PUVA therapy includes the application of a psoralen drug and the administration of light, and both of these have to be adjusted to each other in regard to dose and timing. As psoralens are rather insoluble, it is difficult to produce pharmaceutical formulations which ensure safe and predictable absorption. A strong, saturable first pass effect occurs after oral intake of psoralens, resulting in a wide variability in plasma levels and thus also in phototoxicity. Phototoxicity seems to be slightly delayed compared to plasma levels in the absorption phase, but then persists much longer than plasma levels. Therefore irradiation should be done at or shortly after tmax of plasma levels. "Skin levels" seem to parallel plasma levels rather than the time course of cutaneous photosensitivity, which indicates that they do not represent drug concentration at the true site of action. Metabolism and first pass of TMP are very fast and thus oral intake does not result in significant plasma levels. Phototoxicity may, however, occur if TMP is administered as a solution. The present paper discusses clinically relevant aspects of psoralen drug pharmacokinetics, including absorption, distribution, metabolism and excretion. The shortcomings in the development of regimens for oral psoralen photochemotherapy are pointed out, and suggestions for further developments are given. Based on the pharmacokinetic data, recommendations are given for an improved performance of clinical psoralen photochemotherapy.

Absorption↗
PubMed1984

Pharmacokinetics and pharmacodynamics of psoralens after oral administration: considerations and conclusions.

We discovered a strong but saturable first-pass effect after oral administration of psoralens by using different doses and simultaneous or timed application of stable isotopes. Therefore, small variations of dose, disintegration of drug, and amount and rate of absorption gave rise to great differences in plasma levels and therapeutic efficacy. For practical therapy, the following conclusions can be drawn: 1) Galenical forms of psoralens should ensure a quick and highly reproducible absorption. 2) In the event that inefficacy has been detected, plasma levels should be determined, and the psoralen dosage should be increased rather than the irradiation doses in most instances. 3) For oral psoralen and 320- to 400-nm UV (UVA) treatment, a combination of 5-methoxypsoralen (5-MOP) and 8-MOP (with a lower dose and either administered 30 minutes later than the 5-MOP or in a drug product with quick release of 5-MOP and quick but delayed release of 8-MOP) results in much higher efficacy and reproducibility. Therefore, compared with the single drug, in the combination, dose of drug and the amount of irradiation can be reduced considerably which may result in increased safety. 4) Plasma levels after oral administration of dissolved 4,5',8-trimethylpsoralen are low, but phototoxicity is comparable to that of the 5-MOP and 8-MOP.

Administration, Oral↗
PubMed1983

[Prolapse of the small bowel through the vaginal vault, following hysterectomy].

Within 7 years 4 cases of prolapse of the small bowel through the vaginal vault stump were observed. These occurred between 5 and 10 years following two cases of radical abdominal hysterectomy for cancer and two cases of vaginal hysterectomy and colporrhaphy. The small bowel was replaced three to six hours following the prolapse by median laparotomy. One patient died following late sepsis after the laparotomy.

Aged↗
PubMed1982

Structure and expression of human IFN-alpha genes.

Copy DNA (cDNA) was prepared from induced leucocyte poly(A) RNA and cloned in Escherichia coli. IFN-alpha cDNA clones were isolated by subculture cloning with the use of a translation hybridization assay. Definitive identification of the clones was based on the production of an interferon-like protein by the transformed bacteria. Different IFN-alpha cDNAs, with characteristic target cell specificities, were identified. The cloned cDNAs typically encode a mature polypeptide of 166 (or, for IFN-alpha 2, 165) amino acids and a signal sequence of 23 amino acids. A human chromosomal library was screened with IFN cDNA and 17 distinct IFN-alpha-related sequences were isolated and identified, of which 7 proved to be nonallelic authentic genes and 4 pseudogenes; 6 sequences remain to be elucidated. Taking into account the work of Goeddel and his colleagues, 13 non-allelic authentic genes and 6 pseudogenes can be distinguished. In addition, 9 genes believed to be allelic to the 13 authentic genes have been sequenced. The IFN-alpha genes may be classified into two major subfamilies, which diverged at least 33 Ma ago, but perhaps much earlier, if sequence rectification occurred. At least one IFN-alpha gene appears to have resulted by a recombinational event between members of the subfamily I and II. IFN-beta is distantly related to IFN-alpha's and may have diverged from a common ancestor at least 500 Ma ago. Both IFN-alpha and IFN-beta genes differ from most other genes of higher organisms by being devoid of introns. The mouse was found to possess an IFN-alpha gene family of a size similar to that of man; the murine genes also do not have introns. IFN-alpha genes devoid of their signal sequence were joined to prokaryotic promoters to produce the mature interferons in E. coli in high yield. IFN-alpha 2, purified to homogeneity, has been crystallized by T. Unge and B. Strandberg (Uppsala). Hybrid genes consisting of IFN-alpha 1 and IFN-alpha 2 segments were constructed and expressed in E. coli; the target cell specificities of such hybrids were dependent on the arrangement of the segments and were different from those of either parent. The chromosomal gene for HuIFN-alpha 1 was introduced into mouse L cells to study the mechanism of its expression. Correct transcription was only detected after induction (with Newcastle disease virus); expression was transient, with the same kinetics as those of the endogenous mouse IFN mRNA. Natural murine IFNs and human IFN-beta and IFN-gamma are glycosylated. Because E. coli cells transformed with the genes of eukaryotic glycoproteins are not expected to yield correctly glycosylated polypeptides, we prepared lines of hamster cells permanently transformed with hybrid plasmids, which contained an IFN gene linked to the SV40 early promoter, as well as dihydrofolate reductase as a selective marker. After intracellular amplification of the introduced genes, cell lines were obtained which constitutively produced IFN at about 40 000 units ml-1 and could be propagated for at least several months.

Base Sequence↗
PubMed1982

Assay of bromhexine in human plasma by capillary gas--liquid chromatography with nitrogen-selective detection and selected ion monitoring.

A specific, sensitive method for the determination of bromhexine in human plasma is described. It comprises a selective extraction procedure and a specific determination with capillary gas--liquid chromatography and nitrogen-selective flame ionization detection. The detection limit of the assay is about 0.5 ng/ml. The specificity of the assay was checked by gas chromatography--mass spectrometry. The method is applied to the pharmacokinetics of bromhexine in humans.

Adult↗