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J Lebowitz

Publications and source records attributed to J Lebowitz.

70 records · Page 4Linked to original sources
PubMed1975

Studies of methylmalonyl coenzyme A carbonylmutase activity in methylmalonic acidemia. I. Correlation of clinical, hepatic, and fibroblast data.

Methylmalonyl-CoA carbonylmutase (mutase) activity was measured in fibroblast extracts from 15 patients with methylmalonic acidemia and in extracts of postmortem tissues from 6 of these children. Propionate oxidation and synthesis of 5-deoxyadenosylcobalamin (AdoCbl, the vitamin B12 coenzyme that is part of the mutase holoenzyme) were measured in intact fibroblasts. Mutase activity was low in the absence of added AdoCbl in fibroblast extracts from both control subjects and patients. When the assay included supplemental AdoCbl, mutase activity increased in the control subjects (to 24.0 pmol succinate/mg protein/min) and in extracts from eight of the patients (20.8 pmol/mg protein/min), but showed almost no change in extracts from the other seven patients (0.16 pmol/mg protein/min). We have defined the eight fibroblast lines that showed normal mutase activity in the presence of AdoCbl as "responsive lines" and the other seven lines as "nonresponsive." In the liver or kidney extracts of postmortem tissues, mutase activity responded to AdoCbl supplementation if fibroblast mutase activity from that patient had responded, and failed to respond if fibroblast activity failed to respond. Mean propionate oxidation in intact fibroblasts was much higher in control lines than in either responsive or nonresponsive lines (0.728 vs 0.097 vs 0.080 nmol CO2/10(6) cells/hr, respectively). AdoCbl synthesis was normal (0.27 pg AdoCbl/mg cells wet weight) in nonresponsive fibroblasts but was undetectable (less than 0.005 pg/mg cells) in the responsive lines. Thus, the deficiency of mutase activity in responsive fibroblast lines is due to the failure to synthesize significant amounts of AdoCbl, whereas the deficiency in nonresponsive lines is due to some other abnormality, presumably a defect in the mutase apoenzyme.

Animals↗
PubMed1974

Unpaired bases in superhelical DNA: kinetic evidence.

Kinetic analysis of the early, fast reaction of superhelical DNA with formaldehyde reveals that this region or regions is 56% "single strand like" in character. Hydrogen-tritium exchange studies coupled with other considerations show that this reaction is not due to a difference in conformational motility between form I and form II molecules, but is due to unpaired or weakly hydrogen bonded, localized region(s) of the form I allomorph of circular DNA.

Base Pairing↗
PubMed1974

Locating interrupted hydrogen bonding in the secondary structure of PM2 circular DNA by comparative denaturation mapping.

Previous studies with HCHO have revealed a reaction with superhelical DNA that strongly suggests that this DNA consists of small regions of interrupted secondary structure. To map these sites in PM2 DNA, the following set of experiments was performed using electron microscopy. (i) A denaturation map of nicked form II was obtained using Inman's alkaline-HCHO conditions. (ii) The superhelical form I was reacted with HCHO at 30 C until equilibrium was achieved at the interrupted sites (3.6% reactivity). The excess HCHO was removed rapidly and X-ray treatment was employed to nick these prereacted molecules. These form II molecules containing HCHO (form II HCHO) were also subjected to denaturation mapping. It would be expected that the HCHO-unpaired regions would serve as induction sites for the propagation of melting. Hence, depending on the location of the induction sites; we would anticipate either the creation of new regions of melting or a normal denaturation map shifted to lower pH values. Comparison of the development of progressive denaturation of form II and form II HCHO reveals that the latter is the case. The denaturation maps of form II are highly organized patterns of adenine-thymine (AT)-rich regions, with a total of five regions at extreme pH conditions. There are six highly organized regions for form II HCHO, i.e., smaller adjacent loops, at low denaturation conditions where no denaturation is seen for form II. These coalesce into the pattern for form II containing four of five A-T-rich regions observed for form II. Hence we conclude that the regions of altered hydrogen bonding in superhelical PM2 DNA are four to six in number and they map in the A-T-rich regions of the DNA.

Bacteriophages↗
PubMed1966

Physical and topological properties of circular DNA.

Several types of circular DNA molecules are now known. These are classified as single-stranded rings, covalently closed duplex rings, and weakly bonded duplex rings containing an interruption in one or both strands. Single rings are exemplified by the viral DNA from phiX174 bacteriophage. Duplex rings appear to exist in a twisted configuration in neutral salt solutions at room temperature. Examples of such molecules are the DNA's from the papova group of tumor viruses and certain intracellular forms of phiX and lambda-DNA. These DNA's have several common properties which derive from the topological requirement that the winding number in such molecules is invariant. They sediment abnormally rapidly in alkaline (denaturing) solvents because of the topological barrier to unwinding. For the same basic reason these DNA's are thermodynamically more stable than the strand separable DNA's in thermal and alkaline melting experiments. The introduction of one single strand scission has a profound effect on the properties of closed circular duplex DNA's. In neutral solutions a scission appears to generate a swivel in the complementary strand at a site in the helix opposite to the scission. The twists are then released and a slower sedimenting, weakly closed circular duplex is formed. Such circular duplexes exhibit normal melting behavior, and in alkali dissociate to form circular and linear single strands which sediment at different velocities. Weakly closed circular duplexes containing an interruption in each strand are formed by intramolecular cyclization of viral lambda-DNA. A third kind of weakly closed circular duplex is formed by reannealing single strands derived from circularly permuted T2 DNA. These reconstituted duplexes again contain an interruption in each strand though not necessarily regularly spaced with respect to each other.

Bacteriophages↗
PubMedDate not supplied

Contrast-enhanced hepatic MRI: comparison of half-dose and standard-dose gadolinium DTPA administration in lesion characterization with T1-weighted gradient echo sequences.

The objective of this article was to compare half-dose (0.05 mm/kg) gadolinium-enhanced dynamic hepatic MR imaging to standard doses (0.10 mm/kg). Eighteen patients for follow-up hepatic MR received 0.05 mm/kg of gadolinium DTPA dynamically with gradient-echo imaging. Imaging parameters were identical to a 0.10-mm/kg study; patients were imaged during multiple phases of contrast enhancement. Two readers assessed for enhancement patterns and characterization. Quantitative signal-to-noise ratios (S/N) were obtained for abdominal viscera and contrast-to-noise ratios (C/N) were obtained on up to three lesions. No significant difference for the arterial dominant phase (P > 0.05) was found. Significant differences were found in all categories during the portal venous phase (except pancreas) and equilibrium phase (except liver). Lesion C/N ratios were not significant at any point (P > 0.05). Sixty-two out of 64 lesions (97%) were identically characterized. Therefore, half-dose dynamic gadolinium-enhanced MR may have diagnostic value.

Adult↗
PubMedDate not supplied

Gadolinium-enhanced 3D MRA of the aortic arch vessels in the detection of atherosclerotic cerebrovascular occlusive disease.

PURPOSE: Our goal was to evaluate non-breath-hold Gd-enhanced 3D MR angiography (MRA) for the detection of atherosclerotic occlusive disease of the aortic arch vessels and to compare image quality with two breath-hold techniques. METHOD: One hundred sixty consecutive patients with known or clinically suspected atherosclerotic cerebrovascular occlusive disease underwent Gd-enhanced 3D MRA of the aortic arch and great vessels. One hundred twenty-six examinations were performed with the body coil after infusion of 40 ml of Gd-DTPA; 89 of these were performed without breath-holding and 37 were acquired during suspended respiration. Thirty-four examinations were performed in a body phased-array coil with breath-holding, a timing examination, and 20 ml of contrast agent by manual (n = 17) or power (n = 17) injection. Images were evaluated for the presence of blurring and ghosting artifacts and venous enhancement. Of the 27 patients who underwent non-breath-hold MRI and digital subtraction angiography (DSA), two readers blinded to the DSA results retrospectively evaluated the MRA examinations for the presence of occlusive disease of the innominate, carotid, subclavian, and vertebral arteries. DSA correlation was not evaluated for the 71 breath-hold studies. RESULTS: Sensitivity and specificity for arch vessel occlusive disease with non-breath-hold MRA were 38 and 94% for Reader A and 38 and 95% for Reader B. Breath-holding significantly reduced blurring and ghosting artifacts (p < 0.001) when compared with non-breath-hold imaging, and use of 20 ml of contrast medium, with a timing examination, resulted in significantly less venous enhancement than seen with 40 ml (p < 0.001). CONCLUSION: Non-breath-hold Gd-enhanced 3D MRA is insensitive for detecting arch vessel occlusive disease. Breath-hold imaging, in conjunction with a timing examination and a lower dose of contrast agent, improves image quality, but further studies are needed to assess diagnostic accuracy.

Adult↗