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Biomedical subjects

T Schwartz

Publications and source records attributed to T Schwartz.

At least 37 records · Page 2Linked to original sources
PubMed2000

Management of oculus fragilis in Ehlers-Danlos type VI.

PURPOSE: To describe an alternative, novel surgical approach to the repair of a ruptured globe in the second reported patient with keratoglobus, Ehlers-Danlos type VI, and normal lysyl hydroxylase. METHODS: Under general anesthesia, a 360 degrees conjunctival peritomy was performed and the epithelium was removed from the keratoglobus cornea. Descemet's membrane and endothelium were removed from a fresh donor corneoscleral ring. An onlay epikeratoplasty was then performed and the entire donor corneoscleral button was secured to the sclera with 9-0 nylon suture. The conjunctiva was brought into position and tacked down over the edge of the donor graft. After 4 months, a full-thickness penetrating keratoplasty was then performed. RESULTS: The patient ultimately had a ruptured globe in the fellow eye and thus required the identical procedure OU. Both eyes were successfully repaired with a final visual acuity OU of 20/100. CONCLUSION: The described surgical approach allowed successful surgical repair of bilateral ruptured globes in a patient with keratoglobus, Ehlers-Danlos type VI, and normal lysyl hydroxylase levels. In the previous report of such a patient by Judisch et al. (1), the attempt at surgical repair was unsuccessful and ended in enucleation. The described surgical technique may be used to treat advanced keratoglobus or oculus fragilis.

Child, Preschool↗
PubMed2000

Prednisone and aspirin improve pregnancy rate in patients with reproductive failure and autoimmune antibodies: a prospective study.

PROBLEM: The study was conducted to investigate the efficacy of prednisone and aspirin in autoantibody seropositive patients with repeated in vitro fertilization embryo transfer (IVF ET) failure. METHODS OF STUDY: The study group comprised 52 consecutive patients seropositive for non-organ-specific autoantibodies, i.e., anti-cardiolipin antibodies (ACA), anti-nuclear antibodies (ANA), anti-double-stranded (ds) DNA, rheumatoid factor (RF), and lupus anti-coagulant (LAC). These patients were treated with prednisone, 10 mg per day, and aspirin, 100 mg per day, starting 4 weeks before induction of ovulation in 52 IVF cycles. RESULTS: The clinical pregnancy rate per cycle was 32.7% (17/52). No increased incidence of pregnancy complications, including premature labor, gestational diabetes mellitus, and pregnancy-induced hypertension, were found. CONCLUSIONS: Combined treatment of prednisone for immunosuppression and aspirin as an anti-thrombotic agent, starting before ovulation induction, may improve pregnancy rate in autoantibody seropositive patients who have had repeated IVF-ET failures.

Antibodies, Anticardiolipin↗
PubMed1999

The interaction between Z-DNA and the Zab domain of double-stranded RNA adenosine deaminase characterized using fusion nucleases.

Zab is a structurally defined protein domain that binds specifically to DNA in the Z conformation. It consists of amino acids 133-368 from the N terminus of human double-stranded RNA adenosine deaminase, which is implicated in RNA editing. Zab contains two motifs with related sequence, Zalpha and Zbeta. Zalpha alone is capable of binding Z-DNA with high affinity, whereas Zbeta alone has little DNA binding activity. Instead, Zbeta modulates Zalpha binding, resulting in increased sequence specificity for alternating (dCdG)n as compared with (dCdA/dTdG)n. This relative specificity has previously been demonstrated with short oligonucleotides. Here we demonstrate that Zab can also bind tightly to (dCdG)n stabilized in the Z form in supercoiled plasmids. Binding was assayed by monitoring cleavage of the plasmids using fusion nucleases, in which Z-DNA-binding peptides from the N terminus of double-stranded RNA adenosine deaminase are linked to the nuclease domain of FokI. A fusion nuclease containing Zalpha shows less sequence specificity, as well as less conformation specificity, than one containing Zab. Further, a construct in which Zbeta has been replaced in Zab with Zalpha, cleaves Z-DNA regions in supercoiled plasmids more efficiently than the wild type but with little sequence specificity. We conclude that in the Zab domain, both Zalpha and Zbeta contact DNA. Zalpha contributes contacts that produce conformation specificity but not sequence specificity. In contrast, Zbeta contributes weakly to binding affinity but discriminates between sequences of Z-DNAs.

Adenosine Deaminase↗
PubMed1999

Crystal structure of the Zalpha domain of the human editing enzyme ADAR1 bound to left-handed Z-DNA.

The editing enzyme double-stranded RNA adenosine deaminase includes a DNA binding domain, Zalpha, which is specific for left-handed Z-DNA. The 2.1 angstrom crystal structure of Zalpha complexed to DNA reveals that the substrate is in the left-handed Z conformation. The contacts between Zalpha and Z-DNA are made primarily with the "zigzag" sugar-phosphate backbone, which provides a basis for the specificity for the Z conformation. A single base contact is observed to guanine in the syn conformation, characteristic of Z-DNA. Intriguingly, the helix-turn-helix motif, frequently used to recognize B-DNA, is used by Zalpha to contact Z-DNA.

Adenosine Deaminase↗
PubMed1999

Proteolytic dissection of Zab, the Z-DNA-binding domain of human ADAR1.

Zalpha is a peptide motif that binds to Z-DNA with high affinity. This motif binds to alternating dC-dG sequences stabilized in the Z-conformation by means of bromination or supercoiling, but not to B-DNA. Zalpha is part of the N-terminal region of double-stranded RNA adenosine deaminase (ADAR1), a candidate enzyme for nuclear pre-mRNA editing in mammals. Zalpha is conserved in ADAR1 from many species; in each case, there is a second similar motif, Zbeta, separated from Zalpha by a more divergent linker. To investigate the structure-function relationship of Zalpha, its domain structure was studied by limited proteolysis. Proteolytic profiles indicated that Zalpha is part of a domain, Zab, of 229 amino acids (residues 133-361 in human ADAR1). This domain contains both Zalpha and Zbeta as well as a tandem repeat of a 49-amino acid linker module. Prolonged proteolysis revealed a minimal core domain of 77 amino acids (positions 133-209), containing only Zalpha, which is sufficient to bind left-handed Z-DNA; however, the substrate binding is strikingly different from that of Zab. The second motif, Zbeta, retains its structural integrity only in the context of Zab and does not bind Z-DNA as a separate entity. These results suggest that Zalpha and Zbeta act as a single bipartite domain. In the presence of substrate DNA, Zab becomes more resistant to proteases, suggesting that it adopts a more rigid structure when bound to its substrate, possibly with conformational changes in parts of the protein.

Adenosine Deaminase↗
PubMed1999

Nidovirus infections: experimental model systems of human neurologic diseases.

The presence of terminally differentiated slow- and non-dividing cells in the central nervous system (CNS) provides a safe harbor for viral persistence and latency and constitutes a unique immunologic environment for viral infections. Studies of experimental model systems of viral infections of the CNS provide insight into mechanisms of viral persistence and immune-mediated pathology. Nidoviruses are comprised of 2 families of viruses, coronaviruses and arteriviruses, and are common pathogens of humans and a variety of animal species. Both families of viruses contain neurotropic strains that produce experimental neurologic diseases in rodents. These include acute meningitis and encephalitis; acute poliomyelitis; and chronic inflammatory, immune-mediated, demyelination. Coronavirus-induced demyelinating disease mimics many of the pathologic features of Multiple Sclerosis (MS).

Animals↗
PubMed1999

Crystallization and preliminary studies of the DNA-binding domain Za from ADAR1 complexed to left-handed DNA.

The proteolytically defined Z-DNA binding domain Za of human adenosine deaminase type 1 (hADAR1) has been crystallized in complex with the DNA oligomer d(TCGCGCG). The crystals were obtained from a solution containing ammonium sulfate as precipitating agent and belong to the tetragonal space group P4212. A complete diffraction data set has been collected to a resolution of 2.4 A. The unit-cell dimensions are a = b = 85.9, c = 71.3 A. A Raman spectrum of the complex indicates that the DNA in the complex adopts the left-handed Z conformation.

Adenosine Deaminase↗
PubMed1998

Spectroscopic characterization of a DNA-binding domain, Z alpha, from the editing enzyme, dsRNA adenosine deaminase: evidence for left-handed Z-DNA in the Z alpha-DNA complex.

Double-stranded RNA adenosine deaminase (ADAR1) is an ubiquitous enzyme in metazoa that edits pre-mRNA changing adenosine to inosine in regions of double-stranded RNA. Zalpha, an N-terminal domain of human ADAR1 encompassing 76 amino acid residues, shows apparent specificity for the left-handed Z-DNA conformation adopted by alternating (dGdC) polymers modified by bromination or methylation, as well as for (dGdC)13 inserts present in supercoiled plasmids. Here, a combination of circular dichroism, fluorescence, and gel-retardation studies is utilized to characterize recombinant Zalpha peptide and to examine its interaction with DNA. Results from laser-Raman spectroscopy experiments provide direct evidence for the existence of Z-DNA in peptide-DNA complexes.

Adenosine Deaminase↗
PubMed1998

The Zalpha domain from human ADAR1 binds to the Z-DNA conformer of many different sequences.

Z-DNA, the left-handed conformer of DNA, is stabilized by the negative supercoiling generated during the movement of an RNA polymerase through a gene. Recently, we have shown that the editing enzyme ADAR1 (double-stranded RNA adenosine deaminase, type 1) has two Z-DNA binding motifs, Zalpha and Zbeta, the function of which is currently unknown. Here we show that a peptide containing the Zalpha motif binds with high affinity to Z-DNA as a dimer, that the binding site is no larger than 6 bp and that the Zalpha domain can flip a range of sequences, including d(TA)3, into the Z-DNAconformation. Evidence is also presented to show that Zalpha and Zbeta interact to form a functional DNA binding site. Studies with atomic force microscopy reveal that binding of Zalpha to supercoiled plasmids is associated with relaxation of the plasmid. Pronounced kinking of DNA is observed, and appears to be induced by binding of Zalpha. The results reported here support a model where the Z-DNA binding motifs target ADAR1 to regions of negative supercoiling in actively transcribing genes. In this situation, binding by Zalpha would be dependent upon the local level of negative superhelicity rather than the presence of any particular sequence.

Adenosine Deaminase↗
PubMed1998

Measuring carotid artery stenosis using CT angiography: the dilemma of artifactual lumen eccentricity.

OBJECTIVE: This study assesses artifactual luminal distortion, or eccentricity, that affects measurement of stenosis on CT angiography performed with a variety of helical protocols. MATERIALS AND METHODS: A 32-vessel carotid artery phantom was built with five known grades of stenoses (25%, 50%, 75%, 88%, and 94%) and three lengths of stenosis (1, 3, and 5 mm). This phantom was scanned with conventional and 1.0-, 1.5-, and 2.0-pitch helical CT with slice thicknesses of 2, 4, and 8 mm, and three vessel orientations: parallel, 45 degrees oblique, and perpendicular to the z-axis. Oblique multiplanar reconstruction was performed with the latter two vessel orientations to produce images similar to the parallel to z-axis orientation. The cross-sectional images were then used to measure the maximum and minimum (longest and shortest) luminal diameters in and out of each stenosis at a computer workstation by a single investigator who was unaware of the scanning technique. Percentage of stenosis was assessed by three methods: cross-sectional area in and out of the stenosis, maximum diameter out of stenosis and minimum in stenosis (North American Symptomatic Carotid Endarterectomy Trial method), and minimum diameter in and out of the stenosis. Comparisons were made with the gold standard using the equation (measured percentage of stenosis-actual percentage of stenosis) based on known luminal diameters of the phantom. Luminal eccentricity was assessed for each of the vessels and scanning parameters as a ratio of minimum to maximum diameters. RESULTS: All three methods of measuring stenoses were strongly affected by luminal eccentricity. The North American Symptomatic Carotid Endarterectomy Trial method overestimated percentage of stenosis an average of 1.64%. The most accurate results were obtained when using the minimum diameter in and out of the stenoses (-0.45% from the gold standard). Eccentricity was significantly greater in stenoses than in normal lumen (p < .0001) and when the vessels were oriented perpendicular to the z-axis (p = .0003). A progressive increase in eccentricity was seen in the 4- and 8-mm slice thicknesses and the 3- and 5-mm-long stenoses (p < .001; p < .001). CONCLUSION: Artifactual luminal eccentricity has significant implications for measuring percentage of stenosis revealed by CT angiography. Eccentricity increases in longer stenoses, thicker slices, and vessels oriented perpendicular to the z-axis. With CT angiography, measurement of minimum diameters in and out of a stenosis provides the most accurate assessment of percentage of stenosis.

Artifacts↗
PubMed1997

Peak expiratory flow rate in normal pregnancy.

OBJECTIVE: To determine whether peak expiratory flow rate changes with pregnancy and advancing gestation. METHODS: We measured the peak expiratory flow rate in 57 women during each trimester of pregnancy and postpartum. During four visits, all subjects exhaled forcefully three times into a peak flow meter. For each visit, the best of three attempts defined their peak expiratory flow rate. Using accepted standard nomograms, we normalized peak expiratory flow rate with respect to height and age. Using analysis of variance, we compared the mean normalized peak expiratory flow rates in each of the trimesters and postpartum. RESULTS: The subjects' peak expiratory flow rates did not change significantly during the three trimesters and postpartum (P = .317). The mean peak expiratory flow rates for the three trimesters and postpartum were 434 +/- 18, 452 +/- 16, 444 +/- 15, and 450 +/- 16 (values in liters per minute +/- 95% confidence intervals [CIs]). The mean normalized peak expiratory flow rates for the three trimesters and postpartum were 0.92 +/- 0.036, 0.95 +/- 0.032, 0.94 +/- 0.030, and 0.95 +/- 0.031 (values +/- 95% CI). CONCLUSIONS: This study demonstrates that peak expiratory flow rate does not change with pregnancy and advancing gestation. Therefore, testing peak expiratory flow rate in pregnancy is valid, and physicians can use peak expiratory flow rate accurately and reliably in the management of pregnant women with asthma.

Adolescent↗
PubMed1997

Closure of Pfannenstiel skin incisions. Staples vs. subcuticular suture.

OBJECTIVE: To compare skin closure with staples and subcuticular suture. STUDY DESIGN: Obstetric patients undergoing cesarean section with a Pfannenstiel incision were prospectively randomized to skin closure with staples or subcuticular suture. Pain and cosmesis were assessed postoperatively. RESULTS: Patients reported significantly less pain following subcuticular closure at both the time of discharge (P < or = .01) and the postoperative visit (P < or = .002). Incisions closed with subcuticular suture were found to be more cosmetically attractive by both patients (P = .04) and physicians (P = .01) at the postoperative visit. CONCLUSION: Pfannenstiel skin incisions closed with subcuticular closure following cesarean section result in less postoperative discomfort and are more cosmetically appealing at the six-week postoperative visit as compared to incisions closed with staples.

Cesarean Section↗
PubMed1996

Telomere length does not change during senescence of the ascomycete Podospora anserina.

All strains of the filamentous fungus Podospora anserina are characterized by a well defined life span. Senescence is controlled by nuclear and extranuclear genetic traits. In order to test whether or not the ends of the chromosomes of this ascomycete shorten during senescence and thus telomere shortening may be linked to the well analyzed, age-related reorganizations of the mitochondrial DNA (mtDNA), we analyzed the genomic DNA of P. anserina wild-type strain s. We found that, although the mtDNA becomes reorganized when cultures age, the telomeres remain constant suggesting that telomere shortening does not play a major role in normal aging of this particular biological system.

Ascomycota↗
PubMed1996

Multicenter comparison of micronized fenofibrate and simvastatin in patients with primary type IIA or IIB hyperlipoproteinemia.

In 12 weeks of active treatment, we compared the efficacy and safety of a new (micronized) formulation of fenofibrate (F) (200 mg/day) with that of simvastatin (S) (20 mg/day), an inhibitor of hydroxy-methyl-glutaryl coenzyme A (HMG-CoA)-reductase. Men and women with primary hyperlipoproteinemia (HLP) with low-density lipoprotein (LDL) cholesterol level 180-300 mg/dl and triglyceride level < 500 mg/dl had dietary treatment for 8 weeks, and 133 (2 of 3 type IIa, 1 of 3 type IIb HLP) were randomized. The decrease in total cholesterol differed between type IIa patients (F - 17.9 vs. S - 25.8%), the decrease in triglyceride levels between the type II b groups (F - 52.8 vs. S - 14%), whereas the degree of decrease in LDL cholesterol (F - 20.9 vs. S - 34.9%) differed among all patients. Despite the difference in LDL cholesterol decrease, no difference was noted in total apolipoprotein (apo) B lowering (F - 20.8 and S - 26.5%). Increases in high-density lipoprotein (HDL) cholesterol (F + 18.5 vs. S + 15%) differed specifically in type IIb patients (F + 33.6 vs. S + 11.4%), accompanied by a more pronounced increase in apo AI with fenofibrate (F + 10.5% vs. S no change). Improvement in the ratios of total cholesterol/HDL cholesterol and apo AI/apo B occurred similarly with both drugs. Only fenofibrate, not simvastatin, decreased both fibrinogen (-10.3 vs. + 3.6%) and uric acid (-25% vs. no change) in type IIa and type IIb patients. Safety parameters reflected drug-specific known side effects, underscoring the safety of both drugs in addition to their efficacy in lipid lowering. Besides its advantages in type IIb hyperlipidemia, micronized fenofibrate proved a potent drug in decreasing total and LDL cholesterol and in very effectively decreasing apo B-containing lipoproteins, which is a recommendation for its use in primary hypercholesterolemia.

Adolescent↗
PubMed1995

Mutual adaptation of bacteriophage fd, pfd plasmids and their host strains.

The synthetic plasmid pfdC1 with the replication origin of phage fd and fd gene 2 grows autonomously in E. coli cells. DNA sequencing revealed several mutations compared to the fd genome causing reduced expression of viral gene 2 protein, which can be toxic for the host cell. Another adaptation was noticed for E. coli strains with a copy of fd gene 2 on the F-episome and a pfdA-plasmid with a minimal fd replication origin, when maintained at 42 degrees C. The carrier cells adjusted their cellular metabolism to these stress conditions, whereas replication functions of the plasmid or expression of fd gene 2 on the F-episome were not changed. The filamentous bacteriophages tend to reduce their genome size into miniphages, which was also observed for phages with an antibiotic resistance gene. Bacteriophages with a transposon insertion in the viral gene 2 had a tendency to restore the mutated gene by exchange with the functional gene 2 carried in recA-host cells. Mobilization of pfd-plasmids with RP4 transfer functions was reduced due to interference of replication and transfer in the rolling circle mode. The vectors used in these studies can also be applied as cloning vectors, which are compatible with many other plasmid vectors.

Adaptation, Physiological↗