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D L Daniels

Publications and source records attributed to D L Daniels.

At least 37 records · Page 2Linked to original sources

Investigation of 3,5-isoxazolidinediones as hypolipidemic agents in rodents.

A series of 2-benzoyl-4,4-dialkyl-3,5-isoxazolidinediones proved to have potent hypolipidemic activity, lowering both serum cholesterol and triglyceride levels at 10 or 20 mg/kg/day, IP and orally in rodents. 2-(3,4,5-Trimethoxybenzoyl)-4,4-diethyl-3,5-isoxazolidinedione+ ++ (4) afforded the best hypolipidemic activity lowering normolipidemic CF1 mouse serum cholesterol levels 49% and serum triglyceride levels 34% at 20 mg/kg/day, IP. Compound 4 was selected as a typical derivative of the chemical class for further detailed studies. Serum cholesterol levels in normolipidemic Sprague Dawley male rats were reduced 45% after 8 weeks at 10 and 20 mg/kg/day of compound, orally. Serum triglyceride levels were reduced 38-49% at 10 and 20 mg/kg/day, orally. In vitro liver enzyme activities studies in normolipidemic CF1 mice showed the compound inhibited mitochondrial citrate exchange, acetyl CoA synthetase, HMG CoA reductase, acyl CoA cholesterol acyl transferase, acetyl CoA carboxylase, sn-glycerol-3-phosphate acyl transferase, phosphatidylate phosphohydrolase and heparin-induced lipoprotein lipase activities with increases in the activities of cholesterol ester hydrolase and ATP-dependent citrate lyase. Similar enzyme activities were inhibited in vivo except HMG CoA reductase activity was not inhibited in rat liver or small intestinal mucosa after 8 weeks drug administration. Cholesterol levels were reduced in tissues after 8 weeks administration of compound 4 in normolipidemic rats. Bile cholesterol and triglyceride levels were elevated after two weeks administration to rats at 20 mg/kg/day. Serum lipoprotein levels in normolipidemic and hyperlipidemic rats showed the cholesterol levels in VLDL and LDL fractions after 4, 6 and 8 weeks at 10 and 20 mg/kg/day were reduced whereas HDL-cholesterol levels were significantly elevated. Studies demonstrated that 3H-cholesterol and 14C-palmitic acid incorporation into lipids of the lipoprotein fraction was reduced by the drug but 32P-incorporation was generally elevated. The agent demonstrated no observable toxicity in rats after 8 weeks administration, orally. The acute toxicity study in normolipidemic mice at 20, 40 and 100 mg/kg/day, IP, demonstrated no observable harmful effects of the drug.

Animals↗

Analysis of the Escherichia coli genome. V. DNA sequence of the region from 76.0 to 81.5 minutes.

The DNA sequence of a 225.4 kilobase segment of the Escherichia coli K-12 genome is described here, from 76.0 to 81.5 minutes on the genetic map. This brings the total of contiguous sequence from the E.coli genome project to 725.1 kb (76.0 to 92.8 minutes). We found 191 putative coding genes (ORFs) of which 72 genes were previously known, and 110 of which remain unidentified despite literature and similarity searches. Seven new genes--arsE, arsF, arsG, treF, xylR, xylG, and xylH--were identified as well as the previously mapped pit and dctA genes. The arrangement of proposed genes relative to possible promoters and terminators suggests 90 potential transcription units. Other features include 19 REP elements, 95 computer-predicted bends, 50 Chi sites, and one grey hole. Thirty-one putative signal peptides were found, including those of thirteen known membrane or periplasmic proteins. One tRNA gene (proK) and two insertion sequences (IS5 and IS150) are located in this segment. The genes in this region are organized with equal numbers oriented with or against replication.

Alcohol Dehydrogenase↗

The effect of intracranial surgical trauma on gadolinium-enhanced magnetic resonance imaging.

Gadolinium-enhanced magnetic resonance imaging (MRI) is currently the gold standard for diagnosis of an acoustic neuroma. Its status is diagnosis of a recurrent or residual neuroma is not nearly as clear. A pilot study of 36 postoperative cases showed enhancement in 100% of the patients at the operative site. To examine the role of surgical trauma and biodegradable packing on enhanced MRI, an animal study was designed. Cats and monkeys that underwent posterior fossa surgical procedures had preoperative and postoperative MRI and histologic correlation of any enhanced area. Areas of postoperative enhancement should not be considered as diagnostic of tumor. Further studies are necessary to develop a criteria for recurrent tumor diagnosis with enhanced MRI.

Adult↗

Sequence analysis of four new heat-shock genes constituting the hslTS/ibpAB and hslVU operons in Escherichia coli.

Sequences of four new heat-shock (HS) genes of Escherichia coli organized into two operons were determined. The operon at 83 min specifies two proteins of 15.8 kDa (HslT) and 16.1 kDa (HslS), which are identical to IbpA and IbpB, respectively. Expression of mRNA from a sigma 32-dependent promoter of the hslTS/ibpAB operon is stimulated 30-75-fold upon temperature upshift. The transcription start point (tsp) is located at a G, 96 bp upstream from the AUG start codon of hslT/ibpA. The deduced amino acid sequences of HslT/IbpA and HslS/IbpB are 48% identical to each other and were found to be remotely related to the chloroplast low-molecular-weight HS protein, which is highly conserved among plants. The second hs operon is much less actively stimulated by temperature upshift, although it has a hs promoter that perfectly matches the consensus of promoters recognized by sigma 32. Located at 88.9 min, the hslVU operon specifies proteins of 19.1 kDa (HslV) and 49.6 kDa (HslU). Multiple tsp were found in this operon. HslV is remotely related to the eukaryotic proteasome proteins, and HslU is very similar to a Pasteurella haemolytica protein of unknown function. Both HslU and the P. haemolytica protein share a ATP/GTP-binding motif near their N-termini. The two operons described here are transcribed counterclockwise on the standard genetic map.

ATP-Dependent Proteases↗

Analysis of the Escherichia coli genome. IV. DNA sequence of the region from 89.2 to 92.8 minutes.

We present the sequence of 176 kilobases of the Escherichia coli K-12 genome, from katG at 89.2 to an open reading frame (ORF) of unknown function at 92.8 minutes on the genetic map. This brings the total of contiguous sequence from the E. coli genome project to 500 kb (81.5 to 92.8 minutes). This segment contains 134 putative coding genes (ORFs) of which 66 genes were previously identified. Eight new genes--acs, pepE, and nrfB-G--were identified as well as the previously mapped gldA and alr genes. Still, 58 ORFs remain unidentified despite literature and similarity searches. The arrangement of proposed genes relative to possible promoters and terminators suggests 55 potential transcription units. Other features include 13 REP elements, one IRU (ERIC) repeat, 59 computer-predicted bends, 42 Chi sites and one new grey hole. Sixteen signal peptides were found, including those of lamB, btuB, and malE. Two ribosomal RNA loci, rrnB and rrnE, are located in this segment, so we have now sequenced four of the seven E. coli rRNA loci. Comparison of the rRNA loci reveals some differences in the ribosomal structural RNAs which are generally compatible with the proposed secondary structures.

Base Sequence↗

Genome sequencing on both strands: the Janus strategy.

The design of large scale DNA sequencing projects such as genome analysis demands a new approach to sequencing strategy, since neither a purely random nor a purely directed method is satisfactory. We have developed a strategy that combines these two methods in a way that preserves the advantages of both while avoiding their particular limitations. Computer simulations showed that a specific balance of random and directed sequencing was required for the most efficient strategy, termed the Janus strategy, which has been used in the Escherichia coli genome sequencing project. This approach depended on obtaining sequence easily from either strand of a cloned insert, and was facilitated by inversion of the insert in the engineered M13 vector Janus, by site-specific recombination. The inversion was accomplished simply by growth on the appropriate host strain, when the DNA strand incorporated into the new single stranded phage was complementary to that in the original phage, and was sequenced by the same simple protocol as the first strand.

Bacteriophage lambda↗

Analysis of the Escherichia coli genome. III. DNA sequence of the region from 87.2 to 89.2 minutes.

The DNA sequence of 96.5 kilobases of the Escherichia coli K-12 genome has been determined, spanning the region between rrnA at 87.2 minutes and katG at 89.2 minutes on the genetic map. The sequence includes 84 open reading frames, of which 46 code for unidentified proteins. Six previously mapped but unsequenced genes have been identified in this span: mob, fdhD, rhaD, rhaA, rhaB, and kdgT. In addition, five new genes have been assigned: the heat shock genes hsIU and hsIV, and the genes fdoG, fdoH, and fdoI, which encode the three subunits of formate dehydrogenase-O. The arrangement of the genes relative to possible promoters and terminators suggests 57 potential transcription units. Other features include the precise location of the bacteriophage P2 attachment site attP2II, and eleven REP elements, including one containing 9 REP sequences--one of the largest such elements known. This segment brings the total length of contiguous finished sequence to 325 kilobases.

Base Sequence↗

DNA sequence and analysis of 136 kilobases of the Escherichia coli genome: organizational symmetry around the origin of replication.

The DNA sequence of a 136-kb segment (81.5 to 84.5 min) from the Escherichia coli origin of replication region has been determined and analyzed. Of the 122 protein coding regions that were found, we could assign no gene name or function to half of them, even in this well-studied part of the genome. The newly sequenced region also includes five RNA genes. The arrangement of open reading frames and potential promoters suggests 63 transcription units. The sequence was also analyzed for bend sites and two types of repeated sequence elements. Together with our sequence of the 84.5 to 86.5 min region, this new determination forms a 227-kb contiguous region centered on oriC. A global analysis of this region reveals a remarkable symmetry: most genes are transcribed divergently from the replication origin, and Chi octanucleotide (5'GCTGGTGG3') recombinational hot spots are also strikingly oriented with respect to the directions of replication and translation.

Amino Acid Sequence↗

Global regulation of gene expression in Escherichia coli.

Global transcription responses of Escherichia coli to various stimuli or genetic defects were studied by measuring mRNA levels in about 400 segments of the genome. Measuring mRNA levels was done by analyzing hybridization to DNA dot blots made with overlapping lambda clones spanning the genome of E. coli K-12. Conditions examined included isopropyl-beta-D-thiogalactopyranoside (IPTG) induction, heat shock, osmotic shock, starvation for various nutrients, entrance of cells into the stationary phase of growth, anaerobic growth in a tube, growth in the gnotobiotic mouse gut, and effects of pleiotropic mutations rpoH, himA, topA, and crp. Most mapped genes known to be regulated by a particular situation were successfully detected. In addition, many chromosomal regions containing no previously known regulated genes were discovered that responded to various stimuli. This new method for studying globally regulated genetic systems in E. coli combines detection, cloning, and physical mapping of a battery of coregulated genes in one step.

Adaptation, Physiological↗

Analysis of the Escherichia coli genome: DNA sequence of the region from 84.5 to 86.5 minutes.

The DNA sequence of 91.4 kilobases of the Escherichia coli K-12 genome, spanning the region between rrnC at 84.5 minutes and rrnA at 86.5 minutes on the genetic map (85 to 87 percent on the physical map), is described. Analysis of this sequence identified 82 potential coding regions (open reading frames) covering 84 percent of the sequenced interval. The arrangement of these open reading frames, together with the consensus promoter sequences and terminator-like sequences found by computer searches, made it possible to assign them to proposed transcriptional units. More than half the open reading frames correlated with known genes or functions suggested by similarity to other sequences. Those remaining encode still unidentified proteins. The sequenced region also contains several RNA genes and two types of repeated sequence elements were found. Intergenic regions include three "gray holes," 0.6 to 0.8 kilobases, with no recognizable functions.

Bacterial Proteins↗

The antineoplastic and cytotoxicity of benzohydroxamic acids and related derivatives in murine and human tumor cells.

Benzohydroxamic acids proved to be potent cytotoxic agents suppressing the growth of a number of murine and human cell lines grown in tissue culture, e.g. leukemia, colon, uterine and glioma. Selected compounds demonstrated activity against the growth KB nasopharynx, bronchogenic lung, osteosarcoma and skin cancer. In vivo activity against Ehrlich ascites carcinoma growth was shown with certain compounds. In L1210 cells compound 2 inhibited DNA synthesis significantly within 60 min. the site of action of the agent appears to involve the purine de novo synthesis pathway at PRPP amido transferase and IMP dehydrogenase. Dihydrofolate reductase and nucleoside kinase activities were inhibited by the agent. The levels of d(NTP)s in L1210 cells were reduced after drug treatment. The drug did not appear to affect the DNA template directly causing any damage which might alter transcription and replication nor was there any inhibition of HeLa topoisomerase activity by the drug. Thus the drug appears to be a metabolic inhibitor of nucleoside metabolism.

Animals↗

Visualization of the distal intratemporal facial nerve with MR imaging: use of an oblique plane.

Although magnetic resonance (MR) imaging routinely is used to evaluate the facial nerve, the conventional axial, coronal, and sagittal planes are not optimal for demonstrating the tympanic and mastoid portions of the nerve. A vertical oblique plane for MR imaging of these portions of the facial nerve was evaluated. With this plane, the course of the nerve was effectively demonstrated on MR images and corresponding cryosections. The oblique plane can be used to supplant or supplement conventional planes in imaging of the facial nerve.

Facial Nerve↗

Three-dimensional time-of-flight MR angiography with a surface coil: evaluation in 12 subjects.

We compared three-dimensional time-of-flight MR angiograms obtained with head coils and then with surface coils in five patients with intracranial vascular lesions and in seven normal volunteers to determine if imaging of intracranial vascular anatomy could be improved with the use of a surface coil. Visualization of small peripheral vessels was consistently better with a surface coil than with a head coil at identical small fields of view (FOVs). The surface-coil technique allowed small-FOV imaging of peripheral vascular lesions with higher spatial resolution and signal-to-noise ratio similar to that of large-FOV head-coil images. The use of a surface coil introduced the problem of signal falloff; centrally located vessels were visualized as well or better when a standard head coil was used. We conclude that surface-coil MR angiography can serve as a useful adjunct to routine head-coil MR angiography in the evaluation of peripheral vascular abnormalities.

Angiography↗

High-signal foci on MR images of the brain: observer variability in their quantification.

Foci of high signal in the cerebral white matter are common incidental findings on MR images of the brain of control subjects or patients with a variety of diseases. Although the number of foci has been reported to correlate with age and several risk factors, the degree of observer variability in quantifying foci has not been reported. We used kappa statistics to determine radiologists' agreement in counting high-signal-intensity foci on MR images obtained in healthy volunteers and in patients with hypertension. Before interpreting the images, one pair of radiologists studied 30 routine MR images and reached consensus on differentiating high-signal foci from other foci of high intensity caused by normal structures (e.g., deep gyri or Virchow-Robin spaces). These two observers than independently determined the number of foci in the study group. Using their own criteria, other radiologists independently counted the foci. Agreement between observers was determined with the kappa statistic. The results showed fair agreement between the radiologists who first reached a consensus in counting foci of hyperintensity and poor agreement between the other observers. We conclude that in order to compare the frequency of foci of hyperintensity in different groups of patients, observer variability must be controlled. Studies without proper control subjects may lead to incorrect conclusions regarding the correlation of focal hyperintensities and various risk factors.

Alzheimer Disease↗

Neuroradiology.

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Brain Diseases↗

A study of the association between improved sanitation facilities and children's height in Lesotho.

The impact of improved sanitation on the anthropometric status of children under 5 years in Lesotho was investigated using children recruited into a case-control study of diarrhoea morbidity. The children's height-for-age Z-scores were used as an indicator of chronic undernutrition. Classifying children as 'stunted' or 'adequately nourished' revealed some evidence of an association between latrine ownership and attained height. After allowing for confounding variables, the odds of stunting were 18 per cent lower among children in households with latrines (95 per cent confidence interval, 36 per cent lower to 3 per cent higher). More powerful analyses, using height-for-age as a continuous outcome variable, revealed that the mean height-for-age Z-score of children from households with a latrine was 0.27 standard deviations higher than that of children from households without a latrine (95 per cent c.i. = 0.12 to 0.42). These results suggest that the anthropometric status of children may be as responsive to improvements in sanitation facilities as diarrhoea morbidity in some settings.

Analysis of Variance↗