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P Jank

Publications and source records attributed to P Jank.

8 recordsLinked to original sources
PubMed2002

Pharmacokinetics and metabolism of the anti-oestrogen droloxifene in female human subjects.

1. Single oral doses of a solution formulation of (14)C-droloxifene citrate (141 mg) appeared to be rapidly and well absorbed in four post-menopausal female subjects. Peak plasma concentrations (C(max)) of total (14)C (1260 ng eq. ml(-1)), droloxifene (196 ng ml(-1)) and the major metabolite droloxifene glucuronide (851 ng eq. ml(-1)) occurred at 0.9-1.1 h (T(max)) and declined bi-exponentially with terminal half-lives of 45.0, 31.6 and 32.0 h respectively. The mean AUCs of droloxifene and the major metabolite were 21 and 37% respectively that of total (14)C. 2. Total (14)C was excreted slowly, mainly in the faeces. Mean totals of 6.6 and 90.3% of the dose were excreted in the urine and faeces respectively during 11 days. The data were consistent with biliary excretion and enterohepatic circulation of the major metabolite, droloxifene glucuronide. 3. GC-MS showed that the major (14)C-components in 0-24-h urine were droloxifene (mean 0.4% dose) and its glucuronide (2.3% dose), and in faeces were droloxifene (60.2% dose) and N- desmethyldroloxifene (4.2% dose). Other components in faeces corresponded chromatographically to reference standards, droloxifene N-oxide (1.9% dose), side-chain hydroxylated droloxifene (dimethylamine moiety of droloxifene side-chain replaced by hydroxyl, 1.3% dose) and droloxifene glucuronide (10.7% dose). The latter was resistant to enzymic hydrolysis by the beta-glucuronidase used. 4. Intersubject variability in the pharmacokinetics of droloxifene in this study was relatively low (CV < 20% for AUC and half-life).

Area Under Curve↗
PubMed1982

Nucleotide sequence and secondary structure of citrus exocortis and chrysanthemum stunt viroid.

The complete nucleotide sequence of citrus exocortis viroid (CEV, propagated in Gymura) and chrysanthemum stunt viroid (CSV, propagated in Cineraria) has been established, using labelling in vitro and direct RNA sequencing methods and a new screening procedure for the rapid selection of suitable RNA fragments from limited digests. The covalently closed circular single-stranded viroid RNAs consist of 371 (CEV) and 354 (CSV) nucleotides, respectively. As previously shown for potato spindle tuber viroid (PSTV, 359 nucleotides), CEV and CSV also contain a long polypurine sequence. Maximal base-pairing of the established CEV and CSV sequences results in an extended rod-like secondary structure similar to that previously established for PSTV and as predicted from detailed physicochemical studies of all these viroids. Although the three viroid species sequenced to date differ in size and nucleotide sequence, there is 60--73% homology between them. As PSTV, CEV and CSV also contain conserved complementary sequences which are separated from each other in the native secondary structure. We postulate that the resulting 'secondary' hairpins, being formed and observed in vitro during the complex process of thermal denaturation of viroid RNA, must have a vital, although yet unknown, function in vivo. The possible origin and function of viroids are discussed on the basis of the characteristic structural features and of a considerable homology with U1a RNA found for a region highly conserved in the three viroids.

Base Sequence↗
PubMed1978

Nucleotide sequence and secondary structure of potato spindle tuber viroid.

The viroid of the potato spindle tuber disease (PSTV) is a covalently closed ring of 359 ribonucleotides. As a result of intramolecular base pairing, a serial arrangement of double-helical sections and internal loops form a unique rod-like secondary structure. PSTV is the first pathogen of a eukaryotic organism for which the complete molecular structure has been established.

Base Sequence↗
PubMed1978

Studies on the primary and secondary structure of potato spindle tuber viroid: products of digestion with ribonuclease A and ribonuclease T1, and modification with bisulfite.

Potato spindle tuber viroid (PSTV), a small infectios RNA, has been completely digested with RNase T1 and RNase A, and the resulting oligonucleotides have been sequenced using 5'-terminal 32p-labelling with gamma-32p ATP and T4 polynucleotide kinase, fingerprinting and controlled nuclease P1 digestion. Modified nucleotides have not been detected in 5'-positions of these oligonucleotides. PSTV consists of about 359 nucleotides and contains a remarkable stretch of 18 purines, mainly adenosines; there is no AUG initiation triplet present. The established oligonucleotide sequences preclude a perfect intramolecular base complementarity within the covalently closed viroid circle. Therefore, the rigid, rod-like native secondary structure of PSTV, as seen in the electron microscope, must be based on a defective rather than on a homogeneous RNA helix. The detailed analysis of the bisulfite-catalized modification of cytidine to uridine in PSTV revealed a higher reactivity for the majority of the cytidines than would be expected for a perfect helix. Since only cytidines in single-stranded regions are knonw to be fully reactive, this finding provides additional evidence for defects in the helical secondary structure of PSTV.

Base Sequence↗
PubMed1977

Rabbit liver tRNA1Val:I. Primary structure and unusual codon recognition.

The major valine acceptor tRNA1Val from rabbit liver was purified and its nucleotide sequence determined by in vitro [32P] - labeling with T4 phage induced polynucleotide kinase and finger-printing techniques. Its primary structure was found to be identical with the major valine tRNA from mouse myeloma cells. According to the wobble hypothesis this tRNA, which exclusively has an IAC anticodon, should decode the valine codons GUU, GUC and GUA only. However, this tRNA recognizes all four valine codons with a surprising preference for GUG. It is unknown whether this is due to the lack of A37 modification next to the 3' end of the anticodon IAC. The nature of the inosine-guanosine interaction remains to be clarified.

Animals↗
PubMed1977

Rabbit liver tRNA1Val:II. unusual secondary structure of T psi C stem and loop due to a U54:A60 base pair.

In contrast to all other known tRNAs, mammalian tRNA1Val contains two adenosines A59 and A60, opposite to U54 and psi 55 in the U psi CG sequence of the T psi C loop, which could form unusual A:U (or A: psi pairs in addition to the five "normal" G:C pairs. In order to measure the number of G:C and A:U (A: psi) pairs in the T psi C stem, we prepared the 30 nucleotide long 3'-terminal fragment of this tRNA by "m7G-cleavage". From differentiated melting curves and temperature jump experiments it was concluded that the T psi C stem in this fragment is in fact extended by an additional A60:U54 pair. A dimer of this fragment with 14 base pairs was characterized by gel electrophoresis and by the same physical methods. An additional A:U pair in the tRNA1Val fragment does not necessarily mean that this is also true for intact tRNA. However, we showed that U54 is far less available for enzymatic methylation in mammalian tRNA1Val compared to tRNA from T-E. coli. This clear difference in U54 reactivity, together with the identification of an extra A60:U54 pair in the U psi CG containing fragment suggests the presence of a 6 base pair T psi C stem and a 5 nucleotide T psi C loop in this tRNA.

Adenine Nucleotides↗
PubMed1974

Methyl-deficient mammalian transfer RNA: II. Homologous methylation in vitro of liver tRNA from normal and ethionine-fed rats: ethionine effect on 5-methyl-cytidine synthesis in vivo.

Following hydroxyapatite chromatography, rat liver tRNA methylase activity was assayed with liver tRNA from normal rats and with methyl-deficient liver tRNA from ethionine-fed rats. The difference in homologous methylation between normal and methyl-deficient tRNA was maximal in certain fractions in presence of cadaverine, and much less in presence of Mg(++) or Mg(++) plus cadaverine. These methylase fractions, which contained endogenous tRNA, were used for preparative homologous methylation of added normal and methyl-deficient tRNA in presence of 30 mM cadaverine. The (14)C-methylated tRNA was digested with RNase T(2) and the resulting methylated mononucleotides were characterized and quantitated after twodimensional thinlayer chromatography and autoradiography. The major products of homologous tRNA methylation were m(5)C and m(1)A. However, the methylase fraction used here did not catalyze the formation of m(6) (2)A with m(6) (2)A-deficient tRNA as substrate.- In addition to the previously described, analytically detectable m(6) (2)A-deficiency, a partial m(5)C-deficiency was demonstrated in liver tRNA from ethionine-fed rats by measuring the methylacceptance in vitro. In presence of cadaverine, with the methylase fraction used here, methyl-deficient tRNA from ethionine-fed rats was a twofold more efficient methyl-acceptor in vitro than normal liver tRNA, while endogenous tRNA isolated from the methylase fraction was a threefold more efficient methyl-acceptor than normal liver tRNA. Homologous methylation of normal tRNA, as observed here, has not been described before.

5-Methylcytosine↗