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Biomedical subjects

P Epstein

Publications and source records attributed to P Epstein.

At least 19 recordsLinked to original sources

Viewing the functional consequences of traumatic brain injury by using brain SPECT.

High-resolution brain SPECT is increasingly benefiting from improved image processing software and multiple complementary display capabilities. This enables detailed functional mapping of the disturbances in relative perfusion occurring after TBI. The patient population consisted of 26 cases (ages 8-61 years)between 3 months and 6 years after traumatic brain injury.A very strong case can be made for the routine use of Brain SPECT in TBI. Indeed it can provide a detailed evaluation of multiple functional consequences after TBI and is thus capable of supplementing the clinical evaluation and tailoring the therapeutic strategies needed. In so doing it also provides significant additional information beyond that available from MRI/CT. The critical factor for Brain SPECT's clinical relevance is a carefully designed technical protocol, including displays which should enable a comprehensive description of the patterns found, in a user friendly mode.

Adolescent↗

The precautionary principle in environmental science.

Environmental scientists play a key role in society's responses to environmental problems, and many of the studies they perform are intended ultimately to affect policy. The precautionary principle, proposed as a new guideline in environmental decision making, has four central components: taking preventive action in the face of uncertainty; shifting the burden of proof to the proponents of an activity; exploring a wide range of alternatives to possibly harmful actions; and increasing public participation in decision making. In this paper we examine the implications of the precautionary principle for environmental scientists, whose work often involves studying highly complex, poorly understood systems, while at the same time facing conflicting pressures from those who seek to balance economic growth and environmental protection. In this complicated and contested terrain, it is useful to examine the methodologies of science and to consider ways that, without compromising integrity and objectivity, research can be more or less helpful to those who would act with precaution. We argue that a shift to more precautionary policies creates opportunities and challenges for scientists to think differently about the ways they conduct studies and communicate results. There is a complicated feedback relation between the discoveries of science and the setting of policy. While maintaining their objectivity and focus on understanding the world, environmental scientists should be aware of the policy uses of their work and of their social responsibility to do science that protects human health and the environment. The precautionary principle highlights this tight, challenging linkage between science and policy.

Decision Making↗

The threatened plague.

Explore the source record for details and available documents.

Conservation of Natural Resources↗

Epidemiologists, social scientists, and the structure of medical research on AIDS in Africa.

The development of medical research on AIDS in Africa resembles earlier efforts to understand the epidemiology of TB and syphilis in Africa. In all three cases early research focused on why these diseases exhibited different epidemiological patterns in Africa than in the west. Early explanations of these differences focused on the peculiarities of African behavior, while largely excluding from vision a range of environmental factors. These parallels provide a framework for examining how western ideas about AIDS in Africa developed, the role of social scientists in the formation of these ideas, and how these initial perceptions shaped the subsequent development of AIDS research, encouraging a premature narrowing of research questions. The paper warns that, as in the histories of TB and syphilis research, this early closure may generate inadequate and inappropriate responses to the African AIDS epidemic and limit our understanding of the disease.

Acquired Immunodeficiency Syndrome↗

Tear gas--harassing agent or toxic chemical weapon?

Tear gas has gained widespread acceptance as a means of controlling civilian crowds and subduing barricaded criminals. The most widely used forms of tear gas have been o-chlorobenzylidenemalononitrile and omega-chloroacetophenone. Proponents of their use claim that, if used correctly, the noxious effects of exposure are transient and of no long-term consequences. The use of tear gas in recent situations of civil unrest, however, demonstrates that exposure to the weapon is difficult to control and indiscriminate, and the weapon is often not used correctly. Severe traumatic injury from exploding tear gas bombs as well as lethal toxic injury have been documented. Moreover, available toxicological data are deficient as to the potential of tear gas agents to cause long-term pulmonary, carcinogenic, and reproductive effects. Published and recent unpublished in vitro tests have shown o-chlorobenzylidenemalononitrile to be both clastogenic and mutagenic. Sadly, the nature of its use renders analytic epidemiologic investigation of exposed persons difficult. In 1969, eighty countries voted to include tear gas agents among chemical weapons banned under the Geneva Protocol. There is an ongoing need for investigation into the full toxicological potential of tear gas chemicals and renewed debate on whether their use can be condoned under any circumstances.

Adult↗

Structural organization and chromosomal assignment of the parvalbumin gene.

The structure of the rat parvalbumin gene has been elucidated from analysis of six overlapping clones isolated from a rat lambda Charon 4A genomic library. Two of the clones were mapped in detail, and all exons were localized by Southern hybridization using fragments of a full-length parvalbumin cDNA (Epstein, P., Means, A. R., and Berchtold, M. W. (1986) J. Biol. Chem. 261, 5886-5891). The rat parvalbumin transcription unit is 15.5 kilobase pairs in length and contains four introns. The first intron divides the 5'-nontranslated region, whereas the other three interrupt coding DNA. All intron/extron boundaries were sequenced as was 377 base pairs immediately 5' from the putative transcription initiation site. The promoter region contains eukaryotic regulatory homologies to the "TATA" box at -24 and "CAAT" box at -47 and -156. In addition, two doublets consisting of 11-base pair direct repeats exist in the promoter region. Parvalbumin binds two Ca2+, whereas many other members of the same superfamily bind four. Comparison of the genes that encode these proteins provides a strong confirmation of the hypothesis that parvalbumin evolved from an ancestral gene specifying a four-domain Ca2+-binding protein. The rat parvalbumin gene was also utilized to assign its human counterpart to chromosome 22 from data obtained by hybridization to DNA from a somatic cell hybrid panel. It was also used to isolate a 7.5-kilobase pair EcoRI fragment from a human chromosome 22 DNA library.

Amino Acid Sequence↗

Isolation of a rat parvalbumin gene and full length cDNA.

The complete sequence of the rat parvalbumin mRNA was determined by sequencing a near full length cDNA clone and a primer extension product of the 5' untranslated region of this clone. The parvalbumin sequence contained 72 nucleotides of the 5' untranslated region, 333 nucleotides of the coding sequence, and 183 nucleotides of the 3' untranslated sequence in the case of the shorter parvalbumin messenger RNA or 556 nucleotides in the case of the larger parvalbumin messenger RNA. The two RNAs were derived from a single primary transcript since two clones were sequenced which were identical except for the site of polyadenylation. The polyadenylation signal of the shorter, more abundant RNA was AATAAA while the putative signal for the larger RNA was GATAAA. A 32-base pair sequence comprising part of the 5' untranslated region and the first seven codons of the parvalbumin cDNA was 81% homologous to a region of the chicken calmodulin cDNA encoding part of the first Ca2+-binding domain. This homology indicates that this portion of the parvalbumin mRNA may have evolved from a primordial first domain. A parvalbumin genomic clone which hybridized to probes derived from both the coding and 3' untranslated region of the cDNA was cloned from a rat genomic library. Partial sequencing identified an uninterrupted stretch of 585 base pairs identical to the 3' end of the parvalbumin cDNA. Two introns were localized in the genomic clone. Their position with respect to the parvalbumin amino acid sequence corresponded to the intron locations found in genes of several other Ca2+-binding proteins. This result indicates that, despite the deletion of one Ca2+-binding domain, the remainder of the parvalbumin gene has maintained the structural pattern of the Ca2+-binding protein gene family.

Amino Acid Sequence↗

Simultaneous high-performance liquid chromatography assay of acetylsalicylic acid and salicylic acid in film-coated aspirin tablets.

A reversed-phase high-performance liquid chromatography (HPLC) method has been developed for the simultaneous assay of acetylsalicylic acid (I) and salicylic acid (II) in film-coated aspirin tablets. As little as 0.1% II (relative to I) can be quantitatively determined. Using a 5-microns octadecylsilane column with water-acetonitrile-phosphoric acid (76:24:0.5) as the mobile phase enabled the chromatographic separation to be completed in 4 min. Due to the slow rate of decomposition of I to II in the extraction solvent, acetonitrile-methanol-phosphoric acid (92:8:0.5), the analysis of many samples was routinely performed by means of automated HPLC equipment. Other compounds (non-aspirin salicylates, caffeine and acetaminophen) were also separated by the chromatographic system.

Aspirin↗

Multiple states of U3 RNA in Novikoff hepatoma nucleoli.

U3 RNA, a capped small nuclear RNA found thus far only in the nucleolus, has been implicated in the processing and/or transport of preribosomal RNA [Busch, H., Reddy, R., Rothblum, L., & Choi, Y. C. (1982) Annu. Rev. Biochem. 51, 617-654]. Tris(hydroxymethyl)aminomethane (Tris) (10 mM, pH 7.0) extracts of Novikoff hepatoma nucleoli, which contained about 80% of total nucleolar U3 RNA, were analyzed by sucrose density gradient centrifugation. Approximately 65% of the U3 RNA was bound to greater than 60S preribosomal ribonucleoprotein (RNP) particles, and about 15% sedimented at less than 20 S. The association between the 65% of U3 RNA that was bound to the preribosomal RNP particles was stable up to 55 degrees C. About 10% of U3 RNA was base paired to preribosomal RNA after deproteinization at 22 degrees C. The base-paired fraction of U3 RNA was released from the preribosomal RNA by heating to 45 degrees C or treating with 4 M urea. These results show that of the total nucleolar U3 RNP, (a) about 55% is bound to preribosomal RNP particles primarily by protein interactions, (b) about 10% is base paired to preribosomal RNA, (c) approximately 15% sedimented slowly and consisted presumably of free U3 RNP particles, and (d) the remaining 20% of U3 RNP was not extractable using 10 mM Tris buffer. On the basis of the different association states of U3 RNP particles, a model is proposed for the binding and dissociation events which take place between U3 RNP and preribosomal RNP particles.

Animals↗

Nucleotide sequence of 7 S RNA. Homology to Alu DNA and La 4.5 S RNA.

7 S RNA, a component of normal higher eukaryotic cells and several oncornaviruses, was shown to be conserved in evolution (Erikson, E., Erikson, R. L., Henry, B., and Pace, N. R. (1973) Virology 53, 40-46). Recently, 7 S RNA was shown to be partially complementary to Alu family DNA sequences (Weiner, A. (1980) Cell 22, 209-218). In the present study the nucleotide sequence of Novikoff hepatoma 7 S RNA was determined to be: (formula, see text) Comparison of 7 S RNA, Alu and B1 family DNA, and La 4.5 S RNA sequences for homologies showed that 1) one-third of 7 S RNA, mainly the 5'-end, was homologous to Alu and B1 family sequences; 2) one 300-nucleotide long Alu family sequence contained two binding sites for 7 S RNA; and 3) the 5'-ends of 7 S RNA and La 4.5 S RNA also had extensive (60%) homologies. A model for the secondary structure of 7 S RNA based on maximal base pairing and preferential nuclease cleavage sites is also presented.

Animals↗

Primary and secondary structure of U2 snRNA.

With the improved rapid sequencing techniques, the earlier sequence of U2 RNA of Novikoff hepatoma (Shibata et al, J. Biol. Chem. 250, 3909-3920, 1975) was reanalyzed and modified. The improved sequence of U2 RNA is 188 (or 189) nucleotides long and is in register with a characterized U2 RNA pseudogene (Denison et al, PNAS 78, 810-814, 1981) except for an 11 nucleotide sequence (nucleotides 147-157) which is absent from the pseudogene. From these results, a secondary structure of U2 RNA is proposed which is supported by the preferred cleavage sites with T1-RNase, RNase A and S1 nuclease. Isolated U2 RNA was cleaved by T1-RNase preferentially at positions 64 and 164, whereas U2 RNA in U2-snRNP was cleaved only at position 64, indicating that position 164 is protected in U2-snRNP. As with U1 RNA (Epstein et al, PNAS 78, 1562-1566, 1981) the 5'-end of isolated U2 RNA was not preferentially cleaved by T1-RNase.

Animals↗

Site-specific cleavage by T1 RNase of U-1 RNA in u-1 ribonucleoprotein particles.

The structures and functions of small nuclear ribonucleoprotein particles have become of interest because of their suggested role in processing heterogeneous nuclear RNA [Lerner, M. R., Boyle, J. A., Mount, S. M., Wolin S. L. & Steitz, J. A. (1980) Nature (London) 283, 220-224]. To determine the conformation of U-1 RNA in U-1 ribonucleoprotein particles and whether proteins of these particles protect segments of U-1 RNA, intact particles and isolated U-1 RNA were digested with T1 RNase. The digested particles were immunoprecipitated with anti-Sm antibodies. A 5'-end fragment containing nucleotides 1-107 and 3'-end fragments containing nucleotides 108-165 and 108-153 were recovered in nearly quantitative yield from digestion of the particles, suggesting that position 107 is the principal cleavage site in them. At the same T1 RNase concentrations, deproteinized U-1 RNA was cleaved into many fragments. At low T1 RNase concentrations, major cleavage site of deproteinized U-1 RNA was at nucleotide 69. Comparison of the cleavage sites of free U-1 RNA and of U-1 RNA in U-1 ribonucleoprotein particles suggested similar secondary structures. The resistance of the 5' end of U-1 RNA to T1 RNase was unexpected inasmuch as this region has been implicated in hydrogen bonding with heterogeneous nuclear RNA splice junctions.

Animals↗

The nucleotide sequence of nuclear U6 (4.7 S) RNA.

The low molecular weight RNA species which have been purified and characterized in this laboratory (T.S. Ro-Choi and H. Busch (1974) in The Cell Nucleus, Vol. 3, pp 151-208; Academic Press, New York) are now of interest because of their suggested role in processing of heterogeneous nuclear RNAs (Lerner, M.R., Boyle, J.A., Mount, S.M., Wolin, S.L., and Steitz, J.A. (1980) Nature, 283, 220-224). A previously uncharacterized RNA, U6 (4.7 S) nuclear RNA, which is 106 nucleotides long, was extracted from Novikoff hepatoma ascites cell nuclei and purified by polyacrylamide gel electrophoresis. The primary nucleitde sequence of U6 RNA was determined by subjecting the RNA to several types of enzymatic digestions and gel-sequencing techniques. The sequence is: (formula: see text). U6 RNA contains three pseudouridylic acid residues, four alkali-stable dinucleotides, two alkali-stable trinucleotides, one m6adenosine, and one m2guanosine and is notable for the high concentration of modified nucleotides in the center of the molecule. U6 RNA has an unusual 5' terminus which has not yet been fully characterized.

Animals↗