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Biomedical subjects

J R Levin

Publications and source records attributed to J R Levin.

At least 19 recordsLinked to original sources
PubMed1992

Acute ozone-induced lung injury in neutrophil-depleted rats.

To test the hypothesis that neutrophils contribute to acute, ozone-induced epithelial damage in the lung, rats were depleted of their circulating neutrophils by intraperitoneal injection of a rabbit anti-rat neutrophil serum (ANS) 12 hr prior to an 8-hr exposure to 1.0 ppm ozone. Additional rats were given an injection of normal rabbit serum (NRS) prior to ozone exposure. Exposures were followed by postexposure periods in filtered air for 0, 4, or 16 hr. Control rats were given either ANS or NRS and then exposed only to filtered air. Analysis of bronchoalveolar lavage fluid (BALF) from NRS-treated rats revealed a significant increase in total neutrophils above that of controls at the 4- and 16-hr postexposure times, with a peak increase at 4 hr postexposure. In contrast, there was almost total ablation of the BALF neutrophil response in the ANS-treated rats at all times. Ozone caused an increase in BALF protein, fibronectin, and interleukin-6 above those in controls in both the NRS- and ANS-treated rats, but the only significant difference between the two groups was a level of fibronectin in the neutrophil-depleted animals higher than that in the neutrophil-sufficient animals at the 0-hr postexposure time. Electron microscopic morphometry on lungs fixed by intravascular perfusion demonstrated no significant differences in the volume per surface area epithelial basal lamina (Vs) of necrotic and degenerating epithelial cells in central acini between the neutrophil-depleted and neutrophil-sufficient animals. From these results, we concluded that neutrophils do not play a detectable role in contributing to the early epithelial damage in the lung caused by an acute exposure to ozone.

Animals↗
PubMed1992

Pulmonary inflammation and epithelial injury in response to acute ozone exposure in the rat.

To document the time course of the inflammatory response and epithelial injury in the lung following an acute ozone exposure, rats were exposed to 1.0 ppm ozone for periods between 4 and 24 hr. Some of the exposures were followed by postexposure periods in filtered air for up to 20 hr. Bronchoalveolar lavage fluid (BALF) analysis and electron microscopic morphometry on centriacinar regions of lungs fixed by intravascular perfusion were used to assess the degree of pulmonary inflammation and epithelial cell necrosis. Total protein and numbers of neutrophils and epithelial cells in BALF increased as the duration of ozone exposure increased, while BALF macrophages decreased. Quantitation of the neutrophil response in centriacinar lung regions (capillary, interstitial, and epithelial/luminal compartments of the terminal bronchiole and proximal alveolar duct) by morphometry generally correlated with the BALF analysis, and revealed a greater volume per surface area epithelial basal lamina (Vs) of neutrophils in the terminal bronchiole compartments compared to proximal alveoli. Necrosis of epithelial cells in terminal bronchioles, primarily ciliated cells, occurred as early as 4 hr after initiation of ozone exposure, before marked neutrophil migration, and continued during periods of maximal neutrophil influx. We concluded that the early epithelial necrosis in terminal bronchioles during the first few hours of ozone exposure was primarily due to direct ozone toxicity, but could not rule out the possibility of neutrophils contributing to the injury at later time points, especially between 8 and 12 hr of exposure (during periods of maximal neutrophil migration).

Animals↗
PubMed1991

Relapsing lumbosacral plexus neuropathy. Report of two cases.

Primary lumbosacral plexus neuropathy (LSPN) is a well-defined syndrome characterized by pain, weakness and atrophy in the distribution of the lumbosacral plexus. Previous reports of LSPN have stressed the benign nature of the syndrome. Patients generally have a nearly complete recovery in months to years following the initial event. Two patients presenting with a relapsing form of LSPN are reported. The diagnosis of LSPN was based on clinical and electromyographic features, and no underlying cause was found on initial evaluation or subsequent follow-up over a 6- to 8-year period. We suggest that these patients represent a clinically and possibly pathologically distinct subgroup of LSPN.

Adolescent↗
PubMed1991

Repeated exposures to enzyme-generated oxidants cause alveolitis, epithelial hyperplasia, and fibrosis in hamsters.

Oxidant-mediated epithelial injury and repair processes may promote the development of pulmonary fibrosis. The authors examined this hypothesis by inducing oxidant injury in hamsters with intratracheally instilled mixtures of glucose, glucose oxidase (GO) and lactoperoxidase at weekly intervals. Solutions containing denatured GO (DE) served as a control treatment. One and six days after each treatment, anesthetized animals were sacrificed and lavaged, and their lungs and plasma were preserved for further study. Although DE-treatment consistently evoked a transient, neutrophil-rich inflammatory response, no significant biochemical or morphologic changes were detected at the ensuing 6-day time points. In contrast, repeated GO treatments prolonged inflammation and injured the alveolar epithelium, evidenced by significantly greater levels of neutrophils and macrophages in bronchoalveolar lavage fluid (BALF) and increased BALF levels of protein, beta-glucuronidase and lactic dehydrogenase activities. Active GO also altered BALF lymphocytes and monocytes, but no discernable pattern emerged. Fibrotic, consolidated parenchyma appeared after the second and third GO exposures, coinciding with increased levels of total collagen, prolyl hydroxylase activity, and anti-oxidant enzyme activities. Although alveolitis and type II cell hyperplasia were observed after the initial treatment, polyplike nodules covered by hyperplastic, undifferentiated epithelium were evident after the third treatment. After each exposure, GO-treated animals had larger volumes of parenchymal lesion than DE-treated hamsters. These data indicate that normal alveolar epithelial repair processes were greatly disrupted by repeated oxidant injury and suggest that repeated and/or continued epithelial injury may contribute to the development of pulmonary fibrosis.

Animals↗
PubMed1990

Magnetic resonance imaging correlates of internuclear ophthalmoplegia.

Internuclear ophthalmoplegia (INO) is a gaze disorder characteristic of lesions involving the medial longitudinal fasciculus (MLF). Two patients aged 62 and 74 years presented with acute neurologic deficits characteristic of INO. Computed axial tomography (CT) did not detect abnormalities in the region of the MLF. Magnetic resonance imaging (MRI) however, demonstrated brainstem hypersignals with long T2 characteristics in the region of the MLF which correlated with the clinical symptoms. These cases illustrate the value of the MRI in evaluation of patients with INO and suggest that MRI is superior to CT in evaluating gaze disorders attributable to brain dysfunction.

Aged↗
PubMed1989

Molecular characterization of the Trypanosoma brucei RNA polymerase I and III largest subunit genes.

We have sequenced a 7.1-kilobase fragment of the Trypanosoma brucei RNA polymerase (pol) I largest subunit gene. The 6.9-kilobase transcript from this gene is of roughly equal abundance in bloodstream- and procyclic-form trypanosomes and has a 39-nucleotide trans-spliced leader 290 nucleotides upsteam of the putative initiation codon. The 1781-amino acid trypanosome pol I polypeptide is considerably less similar to its yeast homolog than the trypanosome pol II and pol III polypeptides are to their counterparts in yeast. The yeast and trypanosome pol I polypeptides are distinguished from pol II and pol III largest subunits by two inserts, 100-200 amino acids in length, which are found in the nonconserved portions of the polypeptides. We also report our sequence of the trypanosome pol III largest subunit gene, which agrees with that reported by Köck et al. (Köck, J., Evers, R., and Cornelissen, A.W.C.A. (1988) Nucleic Acids Res. 16, 8753-8772) except for 13 nucleotide differences. Four spliced leader addition sites between 60 and 99 nucleotides upstream of the AUG initiation codon were observed for the 5.4-kilobase transcript from this gene. Four short stretches of amino acid homology between the yeast and trypanosome pol III largest subunit polypeptides were identified which appear to be specific to this class of RNA polymerase; only one short pol I-specific sequence was identified in our comparison of the yeast and trypanosome pol I largest subunit polypeptides.

Amino Acid Sequence↗
PubMed1989

In trypanosomes the homolog of the largest subunit of RNA polymerase II is encoded by two genes and has a highly unusual C-terminal domain structure.

We have isolated the genes encoding the largest subunit of all three classes of RNA polymerase from Trypanosoma brucei. While the pol II largest subunit is encoded by a single gene in all organisms examined to date, trypanosomes contain two copies of the gene. Both genes are expressed in the procyclic and bloodstream stages of the trypanosome life cycle. The two pol II genes differ from one another in their coding sequences by 21 silent substitutions and 4 amino acid substitutions. In the core part of the large subunit, the predicted polypeptides are similar to other eukaryotic RNA polymerases. Both trypanosome pol II polypeptides, like those of other eukaryotes, also have a unique C-terminal extension. However, this domain in the trypanosome polypeptides, unlike those of other eukaryotes, is not a tandemly repeated heptapeptide sequence.

Amino Acid Sequence↗
PubMed1987

Mapping and characterization of transcriptional pause sites in the early genetic region of bacteriophage T7.

During transcription of DNA templates in vitro, Escherichia coli RNA polymerase pauses at certain sequences before resuming elongation. Previous studies have established that some pausing events are brought about by the formation of RNA hairpin structures in the nascent transcript; however, it is not known whether this is an invariant and causal relationship. We have mapped and characterized almost 200 distinct pause sites located within the early region of bacteriophage T7 DNA using a collection of T7 deletion mutant DNAs and taking advantage of a procedure that permits synchronous transcription from the T7 A1 promoter. The pausing pattern is sensitive both to the overall concentration of nucleotide substrates and to the relative concentrations of the four nucleotides. The apparent Ks value for a particular nucleoside triphosphate can vary over a 500-fold range depending on the nucleotide sequence, and pausing at some sites can be induced by modest reductions in substrate concentrations. However, pausing is not solely a consequence of substrate limitation. Pausing at certain sites is caused by some feature of the template or of the transcript itself. Substitution of inosine triphosphate (ITP) for GTP during transcription strongly affects the pattern and strength of pausing events, suggesting that base-pairing interactions involving the RNA strand are important for some pausing events. Other pauses are determined by sequences downstream from the elongation site that have not yet been transcribed, and pausing at these sites is generally insensitive to substitution of IMP for GMP in the nascent transcript. Pausing at one particular site on T7 DNA is strongly enhanced by the presence of E. coli gene nusA protein. These results confirm that there are multiple classes of sites that lead to transcriptional pausing, and provide a collection of sites for further study. Using selected pause sites in the early region of T7 DNA, we have tried to evaluate the possible roles of primary sequence, base composition and secondary structure in pausing. Computer analysis was used to compare primary sequences and potential RNA hairpin structures in transcripts for pauses known to share similar biochemical properties. We see no correlation of pause sites with regions of particular base composition or with specific primary sequences. While some pauses are correlated with the potential to form stable RNA hairpins just upstream from the growing point of the RNA chain, there is not a strict one-to-one relationship between predicted RNA hairpins and the location of pause sites.(ABSTRACT TRUNCATED AT 400 WORDS)

Bacterial Proteins↗
PubMed1987

Isolation and properties of transcribing ternary complexes of Escherichia coli RNA polymerase positioned at a single template base.

We have studied the conditions needed for the formation of stable ternary complexes by Escherichia coli RNA polymerase using a procedure in which elongation by the majority of active enzyme molecules is halted at a specific template base. Stable complexes of this sort, containing RNA chains as short as 15 nucleotides, have been formed from three different promoter sites (T7 A1, lambda PL, and E. coli rrnB P1) using di- and trinucleotides as primers in reactions limited by the presence of only three of the nucleoside triphosphate substrates. The resulting ternary complexes can be stored for at least five days without loss in activity, and provide useful reagents and substrates for studies of the properties of RNA polymerases engaged in chain elongation and termination. At all three promoter sites abortive initiation, leading to synthesis and release of oligomers up to ten nucleotides, competes with productive initiation, leading to the formation of stable elongating complexes. Thus the relative instability of ternary RNA polymerase complexes bearing transcripts shorter than ten nucleotides may be a general feature of the transcription initiation reaction.

Base Sequence↗
PubMed1985

Vocabulary acquisition by mentally retarded students under direct and mnemonic instruction.

Twenty EMR junior-high-school students learned the definitions of unfamiliar English vocabulary words under either direct instruction or mnemonic instruction in a crossover design. When in the mnemonic-instruction condition, students remembered 50% more vocabulary definitions than when they were in the direct-instruction condition. Only three of the 20 students failed to exhibit superior performance when in the mnemonic instruction condition. Supplementary analysis of the response data revealed distinctly different error patterns in the two instructional conditions. In particular, far more intralist intrusions were associated with direct instruction. Implications of these results were discussed.

Adolescent↗
PubMed1976

Motor activity, anticipated motor activity, and young children's associative learning.

The purpose of this study was to determine whether motor activity, previously assumed necessary to induce imagery in young children's associative learning, actually has to be executed. The results of our experiment with kindergartners clearly suggest not: In conditions where subjects simply planned to the potential motor activity (without executing it), learning was enhanced. Further, the temporal proximity of the planning to the potential motor activity did not prove to be important. These results, combined with those from 2 follow-up experiments, give rise to the speculation--among others--that young children can be "tricked" into imagery generation through appropriately worded instructions.

Association Learning↗