Inclusive decay of B mesons into charged D.
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Biomedical subjects
Publications and source records attributed to R Ehrlich.
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Transcription initiation from beta-lactamase, tetracycline resistance and RNA 1 promoters, present in plasmid pAT153, were studied employing the abortive initiation technique. Assays appear to be promoter-specific with supercoiled and linear templates. Supercoiling enhances the isomerization rate constant of the open RNA-polymerase--promoter complex formation. Results agree with the in vivo behaviour of the corresponding promoters, and allow us to propose a hypothesis about the effect of supercoiling on transcription initiation.
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The Kock continent urinary reservoir is a feasible alternative to traditional methods of urinary diversion in properly motivated patients who are anxious to exchange a convenient external appliance for frequent reservoir catheterization. The major shortcomings are increased operative time, loss of a long segment of small bowel, and an approximate 10 percent incidence of major reoperation. Long-term results are unknown. Facility with the operation requires extensive experience and attention to detail. Most complications are related to inadequate fixation of the intussuscepted valves and improper placement of a short terminal segment in the abdominal wall. Early repair of malfunctioning valves and distal segments that are difficult to catheterize is essential to prevent more severe acute complications. Whether the Kock pouch will replace the standard methods of urinary diversion must be determined by more extensive clinical experience and long-term results.
The association of truncus arteriosus with interrupted aortic arch represents a formidable surgical challenge. Two successful repairs have been reported, but none for the past ten years. This report presents a third successful repair using a technique that allows the widely patent ductus arteriosus to maintain continuity between the truncus (with pulmonary arteries detached) and the descending aorta. Right ventricle-pulmonary artery continuity is established in the usual way with a porcine-valved conduit. While long-term potential difficulties with this approach are recognized, it appears to give satisfactory initial palliation and to be an acceptable method of treatment for this combination of defects. The embryology and the anatomy of the lesion are briefly discussed.
Two mutants, mapping at the HindIII site (between the consensus sequences) of the pSC101 tetA promoter, were studied: MA2 corresponds to a 4 bp deletion between positions -12 and -15; B30 bears a 44 bp insertion C(TA)21 G at the HindIII site. Both mutants were assayed in vivo (ability of the plasmid to confer resistance to tetracycline, plasmid-directed protein synthesis, S1-mapping of mRNA) and in vitro (abortive initiation assay). Compared to w.t., MA2 is a poor promoter in vivo; RNA polymerase binding, complex activation and rate of initial oligonucleotide synthesis are strongly reduced in vitro; this is in keeping with the known effects of altering the consensus elements in E. coli promoters. In contrast, B30 shows in vivo a promoter activity only slightly reduced in comparison to that of the w.t. tetA promoter; both in vivo and in vitro, the transcription start site is outside and downstream the (TA)21 stretch, 5-7 bp upstream that found in the w.t. To adjust the behaviour of B30 and the claimed consensus distance between the E. coli promoter consensus sequences, some structural modification in the (TA)21 stretch -either spontaneous or induced by RNA polymerase- can be hypothesized. Unless the (TA)21 stretch itself plays the role of a relatively good promoter, the results suggest that promoter-specific elements may be distributed along the DNA sequences over distances longer, but seldom less, than the 17 +/- 2 bp consensus distance.
Symptoms and signs of severe hypothyroidism developed in a young woman at age 15. These symptoms progressed for a year; at age 16, she was found to have a firm goiter, thyroid autoantibodies, very low serum thyroxine and high thyrotropin values, indicating autoimmune thyroiditis with hypothyroidism. She received L-thyroxine, 0.20 mg per day, and was well until age 24 when she became pregnant. In the first trimester, manifestations indicative of hyperthyroidism developed; these were only ultimately recognized immediately after delivery of a 32-week still-born goitrous baby. Despite the discontinuation of thyroxine therapy, the hyperthyroidism persisted and was confirmed as Graves' disease by elevated thyroxine, triiodothyronine, and radioactive iodine uptake values, a diffuse scanning result, and the presence of thyroid-stimulating antibody. The patient was treated with propylthiouracil and became pregnant while receiving that regimen. Later, several months after delivery, the patient was treated with radioactive iodine, ultimately became hypothyroid, and has been treated ever since with thyroxine. She became pregnant again and, because of the continuing high titers of thyroid-stimulating antibody, received propylthiouracil, 100 mg daily, commencing in the third trimester of pregnancy, to avoid probable fetal hyperthyroidism due to the transplacental transfer of thyroid-stimulating antibody. In each of the last two pregnancies, when the infants were born, they seemed normal (because of the transplacental effect of propylthiouracil), but passive-transfer neonatal hyperthyroidism developed in each within 10 days after delivery, ultimately requiring treatment by conventional means. This case illustrates the following points: (1) Hyperthyroidism occasionally develops years after hypothyroidism. (2) In young women, high titers of thyroid-stimulating antibody may produce fetal and neonatal passive-transfer hyperthyroidism even at a time when the mother herself is no longer hyperthyroid; transplacental treatment of the fetus by maternal propylthiouracil ingestion may thus be necessary during the last trimester, but only when there is a high degree of probability that the fetus is at risk. (3) Because the infants had been protected in utero by the placental transfer of propylthiouracil, neonatal hyperthyroidism did not develop until several days after delivery.(ABSTRACT TRUNCATED AT 400 WORDS)
Three types of natural immune responses against malignant cells were studied in vitro: Cytotoxicity mediated by splenic NK cells; cytostasis mediated by splenocytes and binding of naturally occurring antibodies to various tumour targets. These responses were studied in untreated 3 and 12 month old mice and in mice of both age groups inoculated with B16 melanoma cells. The results showed that in normal mice NK activity decreases with age, cytostatic activity remains unchanged and the titre of natural antibodies increases. Twelve-month old mice were shown to be appreciably more resistant than 3 month old mice to the development of tumours from subthreshold numbers of B16 tumour cells. In mice injected with threshold amounts of the B16 tumour, there was no change in any of the responses in the tumour-free period, but there was a decrease in NK activity and an increase in cytostatic activity when a large tumour mass developed. An increase in the titre of natural antibodies in young mice injected with the tumour was also seen. The correlation between these changes and tumour appearance and development is discussed.
Eukaryotic promoters with known in vivo activities have been analysed for characteristic stability patterns. Correlation of transcription yield in promoter mutants with size and stability of individual domains of the promoter stability profile supports the conclusion that eukaryotic promoters are built up by at least three elements: a region enabling the transcription ("enhancer"), with a characteristic stability pattern; an activator domain, with high GC content, whose activator potential is controlled by the domain stability and length; a trap domain, with high AT content, setting the cap site. The activated enzyme undergoes a steady deactivation process, losing half of its activity upon moving 55 bases between the activator and the trap site.
Analysis of stability maps of sequences harbouring E. coli RNA polymerase promoters shows a characteristic splitting in homostable domains, despite the heterogeneity of the sequences. Correlation of stability maps with results from static approaches giving the contact points of the enzyme on promoters and functional studies employing abortive initiation assay allow us to propose a general mechanism for recognition of promoters and transcription start.
For a series of wild type and mutated eucaryotic gene prelude sequences (mainly "promoters" of SV40 early gene (Benoist and Chambon, Nature 290, 304 (1981); Moreau et al., Nuc. Acids Res. 9, 6047 (1982)) and of Herpes Simplex Virus TK gene (McKnight and Kingsbury, Science 217, 316 (1982)), in vivo promoter activity and local stability (denaturability) have been correlated. In agreement with the conclusions drawn in these papers, the correlation points to three major eucaryotic promoter elements and loci: (i) enzyme enabling by an enhancer sequence; SV40 and Moloney Sarcoma Virus enhancers have a striking stability homology; (ii) enzyme activation, occurring 50-70 b.p. upstream the cap site in a high stability domain; the enzyme apparently deactivates exponentially upon moving away to trap site; (iii) enzyme positioning at trap site, 30 +/- 5 b.p. upstream the cap site. The trap site contains the TATA box, or, when absent, other low stability domains downstream the activator. The number and occupancy of cap sites may depend on the stability and size of the trap site-cap site couple and its distance from the activator.
In this study we determined the effect of administering the chemical carcinogen dimethylbenzanthracene (DMBA) on NK activity mediated by murine splenocytes. The intragastric administration of six weekly 1-mg doses of DMBA to 2- to 3-month-old mice either following a pituitary graft or not, resulted in a tumor incidence which was higher than 60%. The cellularity of the spleens decreased significantly after the third DMBA feeding and the NK activity of these spleens was selectively suppressed. There was no spontaneous reconstitution of the NK activity following cessation of DMBA treatment and during the entire tumor-free period. The adoptive transfer of normal bone marrow, thymus or spleen cells did not restore NK activity in DMBA-treated mice. The NK activity of DMBA-fed mice could be augmented by interferon and by interferon inducers such as poly I:C and dsRNA from Ustilago virus. The effect of these biological response modifiers on NK activity was short-lived but it was possible to restimulate this activity every 24 h. Consecutive treatments of DMBA-fed mice with poly I:C maintained a high level of NK activity for at least 3 weeks.
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Experience with the prenatal diagnosis and management of four cases of congenital renal abnormalities is presented. Neither prenatal intervention nor early delivery was indicated in any of these patients. The current enthusiasm for aggressive management of fetal renal abnormalities may underestimate difficulties in prenatal diagnosis and overestimate the potential benefits of early intervention.
The signal qualifying an AUG or GUG as an initiator in mRNAs processed by E. coli ribosomes is not found to be a systematic, literal homology sequence. In contrast, stability analysis reveals that initiators always occur within nucleic acid domains of low stability, for which a high A/U content is observed. Since no aminoacid selection pressure can be detected at N-termini of the proteins, the A/U enrichment results from a biased usage of the code degeneracy. A computer analysis is presented which allows easy detection of the codon strategy. N-terminal codons carry rather systematically A or U in third position, which suggests a mechanism for translation initiation and helps to detect protein coding sequences in sequenced DNA.
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