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Biomedical subjects

J E Mueller

Publications and source records attributed to J E Mueller.

At least 19 recordsLinked to original sources

Maternal oral contraceptive use and atopic diseases in the offspring.

BACKGROUND: This study examined the association of maternal oral contraceptive (OC) use - before and after birth - and atopic manifestations in the offspring. METHODS: A total of 2754 East German children aged 5-14 years participated in a cross-sectional survey in 1998-99. The standardized parental questionnaire in 1998-99 included data on atopic diseases, socio-economic factors, parental atopy and maternal OC use. Specific immunoglobulin E against common inhalant allergens was measured by radioallergosorbent test (RAST). RESULTS: Maternal OC use before birth was associated with a higher risk of atopic diseases in the offspring compared with children of mothers who had never taken OC [asthma: odds ratio (OR) 1.6; 95% confidence interval (CI): 0.9-3.0; allergic rhinitis: OR 1.5; CI: 0.96-2.2; atopic eczema: OR 2.6; CI: 1.6-4.3; atopic sensitization: OR 1.5; CI: 0.97-2.2]. However, the effect estimates for maternal OC use after birth compared with the never users showed quite similar effects for these atopic conditions. No relations were observed between the prevalences of atopic diseases and maternal age at beginning of OC use, the duration of OC use, the type of contraceptive or maternal age at birth. CONCLUSION: This study raises doubts in a true biological association between OC use and atopic diseases.

Adolescent↗

The musculocutaneous sural artery flap for soft-tissue coverage after calcaneal fracture.

Soft-tissue defects following calcaneal fractures can be covered in a relatively easy and safe procedure. We have modified the familiar distally based sural artery flap by lifting a part of the gastrocnemius muscle. With an inferior pedicle, this musulocutaneous flap can be rotated onto the defect on the sole of the foot and on the heel. Five patients with open fractures of the calcaneus or wound necrosis after osteosynthesis were treated with this procedure. Two defects were covered uneventfully, two flaps were prepared, the rotation being done in a secondary procedure. One patient demanded further revisions, and the flap was partially lost, but the remaining defect was covered after open treatment. This new musculocutaneous sural artery flap can be used for covering even an extensive defect after calcaneal fractures and seems to be a reliable procedure. Morbidity at the donor site is low, and in the case of failure, the free flap remains an alternative.

Calcaneus↗

Low levels of estradiol are associated with vertebral fractures in older men, but not women: the Rancho Bernardo Study.

This longitudinal study included 288 postmenopausal women without estrogen use (median age, 72 yr) and 352 men (median age, 66 yr). All were community-dwelling, ambulatory, and Caucasian. Blood for hormone assays (total and bioavailable estradiol and testosterone, estrone, androstenedione, dihydrotestosterone, dehydroepiandrosterone, and dehydroepiandrosterone sulfate) was obtained in 1984-1987, and vertebral fractures were diagnosed from lateral spine radiographs obtained in 1992-1996. At least one vertebral fracture was found in 21% of women and 8% of men. Among men, age-adjusted hormone levels differed by fracture status only for total (64.1 vs. 75.4 pmol/L, P = 0.012) and bioavailable (43.0 vs. 51.4 pmol/L, P = 0.008) estradiol. There was a graded association between higher concentrations of total and bioavailable estradiol and lower fracture prevalence (trend P<0.01 for both hormones). Men with total testosterone levels compatible with hypogonadism (<7 nmol/L) were not more likely to have vertebral fractures. In women, none of the measured sex hormones was associated with vertebral fractures. There was also no increased prevalence of fractures in women with estradiol levels below the assay sensitivity (<11 pmol/L). These data suggest that estrogen plays a critical role in the skeletal health of older men and confirm other studies showing no association of postmenopausal endogenous estrogen levels with vertebral fractures in older women.

Age Factors↗

Retrohoming of a bacterial group II intron: mobility via complete reverse splicing, independent of homologous DNA recombination.

The mobile group II intron of Lactococcus lactis, Ll.LtrB, provides the opportunity to analyze the homing pathway in genetically tractable bacterial systems. Here, we show that Ll.LtrB mobility occurs by an RNA-based retrohoming mechanism in both Escherichia coli and L. lactis. Surprisingly, retrohoming occurs efficiently in the absence of RecA function, with a relaxed requirement for flanking exon homology and without coconversion of exon markers. These results lead to a model for bacterial retrohoming in which the intron integrates into recipient DNA by complete reverse splicing and serves as the template for cDNA synthesis. The retrohoming reaction is completed in unprecedented fashion by a DNA repair event that is independent of homologous recombination between the alleles. Thus, Ll.LtrB has many features of retrotransposons, with practical and evolutionary implications.

Bacterial Proteins↗

Exon coconversion biases accompanying intron homing: battle of the nucleases.

Intron homing in phage T4 occurs in the context of recombination-dependent replication, by virtue of intron-encoded endonucleolytic activity. After the td intron endonuclease I-TevI cleaves the intronless recipient 23 and 25 nucleotides upstream of the intron insertion site, exonucleolytic degradation is required for recombination to proceed. This resection process results in coconversion of exon sequences flanking the intron. In a genetic system designed to study coconversion of flanking markers, we demonstrate that although there is a bidirectional polarity gradient, coconversion can be highly asymmetric. Furthermore, we show that the coconversion of flanking markers favors exon I sequences, upstream of the I-TevI cleavage site. These data are consistent with the asymmetric features of the homing pathways that have been invoked for intron mobility in phage T4. Moreover, these results are in accord with the finding that once the td homing-site substrate is cleaved, I-TevI remains bound to the downstream cleavage product, protecting against exonucleolytic degradation, and thereby limiting the extent of coconversion into exon II. The results suggest that recombination events are influenced by a competition between the homing endonuclease and exonucleases for sequences downstream of the I-TevI cleavage site, thereby implying a role for the homing endonuclease in the repair process.

Bacteriophage T4↗

Intron mobility in phage T4 occurs in the context of recombination-dependent DNA replication by way of multiple pathways.

Numerous group I introns in both prokaryotes and eukaryotes behave as mobile genetic elements. The functional requirements for intron mobility were determined in the T4 phage system using an in vivo assay to measure intron homing with wild-type and mutant derivatives. Thus, it was demonstrated that intron mobility occurs in the context of phage recombination-dependent replication, a pathway that uses overlapping subsets of replication and recombination functions. The functional requirements for intron homing and the nature of recombinant products are only partially consistent with the accepted double-strand-break repair (DSBR) model for intron inheritance, and implicate additional homing pathways. Whereas ambiguities in resolvase requirements and underrepresentation of crossover recombination products are difficult to rationalize strictly by DSBR, these properties are most readily consistent with a synthesis-dependent strand annealing (SDSA) pathway. These pathways share common features in the strand invasion steps, but differ in subsequent repair synthesis and resolution steps, influencing the genetic consequences of the intron transfer event.

Bacteriophage T4↗

Intron-encoded endonuclease I-TevI binds as a monomer to effect sequential cleavage via conformational changes in the td homing site.

I-TevI, the intron-encoded endonuclease from the thymidylate synthase (td) gene of bacteriophage T4, binds its DNA substrate across the minor groove in a sequence-tolerant fashion. We demonstrate here that the 28 kDa I-TevI binds the extensive 37 bp td homing site as a monomer and significantly distorts its substrate. In situ cleavage assays and phasing analyses indicate that upon nicking the bottom strand of the td homing site, I-TevI induces a directed bend of 38 degrees towards the major groove near the cleavage site. Formation of the bent I-TevI-DNA complex is proposed to promote top-strand cleavage of the homing site. Furthermore, reductions in the degree of distortion and in the efficiency of binding base-substitution variants of the td homing site indicate that sequences flanking the cleavage site contribute to the I-TevI-induced conformational change. These results, combined with genetic, physical and computer-modeling studies, form the basis of a model, wherein I-TevI acts as a hinged monomer to induce a distortion that widens the minor groove, facilitating access to the top-strand cleavage site. The model is compatible with both unmodified DNA and glucosylated hydroxymethylcytosine-containing DNA, as exists in the T-even phages.

Base Sequence↗

Selection of a remote cleavage site by I-tevI, the td intron-encoded endonuclease.

I-TevI, a double-strand DNA endonuclease involved in the mobility of the td intron of phage T4, is highly unusual in that it binds and cleaves intronless td alleles (td homing sites) in a site-specific but sequence-tolerant manner. The endonuclease binds to sequences flanking the intron insertion site and near the remote cleavage site, located 23 and 25 nucleotides away on the top and bottom strands, respectively. Mapping studies indicate that I-TevI has both sequence and distance sensors that function during cut-site selection. Although I-TevI cleavage of many insertion and deletion variants of the homing site is impaired, double-strand breaks are generated at positions that collectively span two turns of the helix, indicating that the interaction is extraordinarily flexible. However, the endonuclease does exhibit spacing preferences between its binding domains, and sequence preferences near the cleavage site, with the G:C pair at -23 implicated as a cleavage determinant. Furthermore, I-TevI appears to function through interactions across the minor groove at the cleavage site, as it does at the intron insertion site, and to be capable of cleaving sequentially, first on the bottom and then on the top strand. These properties of I-TevI are incorporated in a model wherein the endonuclease effects distant cleavage via a flexible hinge.

Bacteriophage T4↗

[Preserving the length of amputation stumps by microvascular flap transfer of the lower extremity].

With different case reports we want to show the role of microvascular tissue transfer in preservation of lower extremity amputation length. To salvage amputation stumps after traumatic amputation, as well as in case of chronic soft tissue problems after amputation, the radialis forearm flap is preferred for smaller defects, for example after transmetatarsal amputation, whereas with the latissimus dorsi muscle flap bigger areas can be reconstructed. But also the tensor fascia latae flap and the scapular flap can be used for soft tissue reconstruction. With microvascular soft tissue transfer amputation stump length can be preserved in order to have a better functional outcome, especially for prosthetic rehabilitation.

Adolescent↗

The td intron endonuclease I-TevI makes extensive sequence-tolerant contacts across the minor groove of its DNA target.

I-TevI, a double-strand DNA endonuclease encoded by the mobile td intron of phage T4, has specificity for the intronless td allele. Genetic and physical studies indicate that the enzyme makes extensive contacts with its DNA substrate over at least three helical turns and around the circumference of the helix. Remarkably, no single nucleotide within a 48 bp region encompassing this interaction domain is essential for cleavage. Although two subdomains (DI and DII) contain preferred sequences, a third domain (DIII), a primary region of contact with the enzyme, displays much lower sequence preference. While DII and DIII suffice for recognition and binding of I-TevI, all three domains are important for formation of a cleavage-competent complex. Mutational, footprinting and interference studies indicate predominant interactions of I-TevI across the minor groove and phosphate backbone of the DNA. Contacts appear not to be at the single nucleotide level; rather, redundant interactions and/or structural recognition are implied. These unusual properties provide a basis for understanding how I-TevI recognizes T-even phage DNA, which is heavily modified in the major groove. These recognition characteristics may increase the range of natural substrates available to the endonuclease, thereby extending the invasive potential of the mobile intron.

Base Sequence↗

Assembly and characterization of five-arm and six-arm DNA branched junctions.

DNA branched junctions have been constructed that contain either five arms or six arms surrounding a branch point. These junctions are not as stable as junctions containing three or four arms; unlike the smaller junctions, they cannot be shown to migrate as a single band on native gels when each of their arms contains eight nucleotide pairs. However, they can be stabilized if their arms contain 16 nucleotide pairs. Ferguson analysis of these junctions in combination with three-arm and four-arm junctions indicates a linear increase in friction constant as the number of arms increases, with the four-arm junction migrating anomalously. The five-arm junction does not appear to have any unusual stacking structure, and all strands show similar responses to hydroxyl radical autofootprinting analysis. By contrast, one strand of the six-arm junction shows virtually no protection from hydroxyl radicals, suggesting that it is the helical strand of a preferred stacking domain. Both junctions are susceptible to digestion by T4 endonuclease VII, which resolves Holliday junctions. However, the putative helical strand of the six-arm junction shows markedly reduced cleavage, supporting the notion that its structure is largely found in a helical conformation. Branched DNA molecules can be assembled into structures whose helix axes form multiply connected objects and networks. The ability to construct five-arm and six-arm junctions vastly increases the number of structures and networks that can be built from branched DNA components. Icosahedral deltahedra and 11 networks with 432 symmetry, constructed from Platonic and Archimedean solids, are among the structures whose construction is feasible, now that these junctions can be made.

Base Sequence↗

Characterization of a bimobile DNA junction.

We present here a chemical and enzymatic footprinting analysis of a branched DNA molecule formed from four complementary 50-mer strands. These strands are designed to form a stable junction, in which two steps of branch point migration freedom are possible. Exposure of the junction to Fe(II).EDTA shows protection of 3 or 4 residues in each strand at the branch, while two resolvase enzymes (endonuclease VII from phage T4 and endonuclease I from phage T7), cleave all four strand near the branch. Chemical footprinting of this junction using the reagents MPE.Fe(II) and (OP)2Cu(I) shows that the branch site is hyper-reactive to cutting induced by these probes as it is in an immobile four-arm junction. The effects involve more residues than in the immobile case. In the absence of divalent cations, the structure of the junction alters, sites of enhanced cleavage by MPE.Fe(II) and (OP)2Cu(I) disappear, and purines at the branch become reactive to diethyl pyrocarbonate. Our interpretation of these results is based on the properties of immobile junction analogs and their response to these probes. In the presence of Mg2+, the three migrational isomers coexist, each probably in the form of a 2-fold symmetric structure with two helical arms stacked.

Base Sequence↗

Resolution of Holliday junction analogs by T4 endonuclease VII can be directed by substrate structure.

Endonuclease VII is an enzyme from bacteriophage T4 capable of resolving four-arm Holliday junction intermediates in recombination. Since natural Holliday junctions have homologous (2-fold) sequence symmetry, they can branch migrate, creating a population of substrates that have the branch point at different sites. We have explored the substrate requirements of endonuclease VII by using immobile analogs of Holliday junctions that lack this homology, thereby situating the branch point at a fixed site in the molecule. We have found that immobile junctions whose double-helical arms contain fewer than nine nucleotide pairs do not serve as substrates for resolution by endonuclease VII. Scission of substrates with 2-fold symmetrically elongated arms produces resolution products that are a function of the particular arms that are lengthened. We have confirmed that the scission products are those of resolution, rather than nicking of individual strands, by using shamrock junction molecules formed from a single oligonucleotide strand. A combination of end-labeled and internally labeled shamrock molecules has been used to demonstrate that all of the scission is due to coordinated cleavage of DNA on opposite sides of the junction, 3' to the branch point. Endonuclease VII is known to cleave the crossover strands of Holliday junctions in this fashion. The relationship of the long arms to the cleavage direction suggests that the portion of the enzyme which requires the minimum arm length interacts with the pair of arms containing the 3' portion of the crossover strands on the bound surface of the antiparallel junction.

Base Sequence↗

T4 endonuclease VII cleaves the crossover strands of Holliday junction analogs.

We have formed four-arm branched DNA junctions that contain no more than a single base pair of branch migratory freedom. Recently, we have shown that these Holliday junction analogs have twofold symmetric protection patterns in solution when probed with hydroxyl radicals: two opposite strands of one junction show extensive protection near the branch point, while the other pair of opposite strands is virtually as susceptible as a double helix. In a different junction, the hydroxyl radical protection pattern is reversed. These patterns suggest that a crossover-isomer bias exists in these molecules and that the protected strands form the crossover between helices. Here, we examine the cleavage pattern of these structures when they are resolved by T4 endonuclease VII. Junctions are formed from a single shamrock-shaped molecule, which contains 5', 3', or internal labels. The enzyme shows a preference for resolving these modified junctions at sites near those protected from hydroxyl radicals. This result suggests that only crossover strands in a Holliday junction are cleaved, and thus an odd number of crossover isomerizations must occur when flanking markers are exchanged.

Base Sequence↗

A bibliography of doctoral dissertations on aging from American institutions of higher learning, 1981-1983.

This bibliography is the thirteenth supplement to the original work which covered 1934-1969. The supplements include all titles of earlier years which were found after the original bibliography was published in the Journal of Gerontology, 1971, 26, 391-422. Due to the nature of bibliographic control in regard to doctoral dissertations, each supplement will try to cover the academic year rather than the calendar year. This means that a dissertation issued in 1970 may be either in the original bibliography or in the supplements. Both online and manual search techniques were employed in the compilation of this supplement. The arrangement of the supplement is similar to the original bibliography.

Academic Dissertations as Topic↗

A bibliography of doctoral dissertations on aging from American institutions of higher learning, 1979-1981.

This bibliography is the eleventh supplement to the original work which covered 1934-1969. The supplements include all titles of earlier years which were found after the original bibliography was published, Journal of Gerontology, 1971, 26, 391-422. Due to the nature of bibliographic control in regard to doctor dissertations, each supplement will try to cover the academic year rather than the calendar year. This means that a dissertation issued in 1970 may be either in the original bibliography or in the supplements. Both online and manual search techniques were employed in the compilation of this supplement. The arrangement of the supplement is similar to the original bibliography.

Academic Dissertations as Topic↗