Opponent-process theory and drug conditioning: an assessment for conditioned stimulant-induced movement. Opponent-process theory occupies an important place in drug conditioning because it accounts for conditioned drug effects which are opposite to those induced by the drug itself. It has not been established, however, whether there is an opponent-process component to stimulant drug induced conditioned effects. In the present study the unilateral 6-hydroxydopamine (6-OHDA) rat model was used to examine this issue. Two groups of Sprague-Dawley rats with equivalent 6-OHDA lesions were administered five apomorphine treatments (0.05 mg/kg s.c.) either paired or unpaired to a 10-min test chamber placement. Apomorphine induced vigorous contralateral rotation and suppressed all ipsilateral rotation. While the apomorphine-induced contralateral rotation response can be conditioned to the test environment cues, the critical test of opponent-process theory in the present study was whether the opposite response of ipsilateral rotation would also become conditioned as a latent opponent-process response to the exteroceptive test environment cues associated with the apomorphine drug state. The postacquisition saline test for conditioning showed that the paired group exhibited higher rates of contralateral and ipsilateral rotation compared to the unpaired group. In addition, when the animals were subsequently tested with the dopaminergic receptor antagonist, haloperidol (0.5 mg/kg), unexpectedly, contralateral rotation was enhanced in the paired group, whereas, ipsilateral rotation was suppressed in both groups. While these findings are, in part, compatible with an opponent-process mechanism, the data supported a simpler explanation; namely, the mechanism of differential habituation in the two groups due to a blocking effect of apomorphine on habituation selectively in the paired group.(ABSTRACT TRUNCATED AT 250 WORDS)


Hippocampal mossy fibres: implication in novelty reactions or in anxiety behaviours? Hippocampal mossy fibre distribution is known to correlate with various processes including responses to novelty. Unfortunately, these correlations have been calculated using behavioural variables recorded in situations including anxiogenic components and so it is not clear whether the hippocampal trait is related to novelty reactions or to anxiety. In order to better elucidate the functional role of the supra- (SP-MF), intra-infra-(IIP-MF) and dentate gyrus (CA4) mossy fibres synaptic area, we investigated their covariations with behavioural measures recorded in situations related to novelty (free exploration test, confrontation with a novel object) or to anxiety (light/dark choice test). The hippocampus-behaviour correlation matrix reveals that IIP-MF and SP-MF correlate with variables linked to novelty reactions while CA4 correlates with measures related to anxiety.


Learning behaviour in chronic vitamin E-deficient and -supplemented rats: radial arm maze learning and passive avoidance response. The effects of long-term vitamin E deficiency and supplementation on learning behaviour were investigated. Rats were fed vitamin E-deficient [VE(-)], -supplemented [VE(+)], or control standard food beginning after the age of 4 weeks. They were trained in an eight-arm radial maze learning task at the age of 17 months, and in a step-through passive avoidance response (PAR) task at the age of 25 months. In the radial maze task, both VE(-) and VE(+) animals required as many trials to reach the learning criterion as control animals. Scopolamine injection (0.25-0.5 mg/kg) after acquisition of the task decreased the number of correct choices dose-dependently; however, the degree of the drug effect on VE(-) and VE(+) rats did not differ from that on control rats. On the other hand, VE(-) animals showed significantly lower rate of avoidance response and VE(+) animals tended to show higher rate of avoidance response in the PAR task than did control animals. These results suggest that long-term vitamin E deficiency or supplementation does not influence general ability to acquire and maintain memory tasks in rats, but that it may affect learning behaviour, depending on the kind of task in which animals were trained.


Effects of CGS 19755 and dizocilpine (MK 801) on delayed time discrimination performance. The effects of the competitive NMDA (N-methyl-D-aspartate) receptor antagonist CGS 19755 and the non-competitive NMDA receptor antagonist dizocilpine (MK 801) on time discrimination and short-term memory were investigated in rats trained on a delayed time discrimination task. In a two-lever operant chamber, pressing one lever was correct and reinforced with a food pellet after presentation of a stimulus light for 2 s (SD(short)); pressing the opposite lever was correct after presentation of a stimulus light for 8 s (SD(long)). CGS 19755 (3.0 mg/kg) attenuated performance, decreased nose-pokes (an activity necessary to trigger the presentation of the discriminative stimulus and the presentation of the response levers), and increased response latencies (time from 'opportunity to leverpress' to 'actual leverpress'). The highest dose of dizocilpine (0.2 mg/kg) tested also attenuated performance. Further, the number of nose-pokes and response latencies were not altered by any dose of dizocilpine. With increasing delays, saline-injected animals developed a bias towards reporting an occurrence of an SD(long), independent of the actual stimulus presented. This bias was attenuated or even reversed by CGS 19755 (3.0 mg/kg) and (0.2 mg/kg). Our results suggest that NMDA receptors are directly or indirectly involved in time discrimination performance.


Retrieval of active and inactive visual discriminations while temporal cortex is suppressed with cold. While local cooling of inferotemporal cortex (IT) impairs new visual learning, it has little effect on recall. However, in visual discriminations, there is typically extensive exposure to the stimuli before cortical inactivation. Perhaps if recall was prevented before suppression, it would fail during suppression. Three animals with cryodes covering a major part of IT were trained on two face discriminations. They were then run on one of these discriminations for 3 days to create the expectation that the task would be continued with the same stimuli, and on the 4th day, they were started with these stimuli, but after cold suppression, they were switched to a discrimination that they should not have anticipated. IT suppression prevented recall of the discrimination that had not been pre-exposed; performance dropped to chance and stayed there for 50 trials. When they were switched back to the initial pair, performance returned nearly to normal. The experiment was repeated with the role of anticipated and unanticipated stimuli reversed. It was suggested that pre-exposure to the discrimination created the expectation that the same stimuli would continue to be used, and induced information about them to be copied from IT into prestriate cortex.


Visual performance of pigeons following hippocampal lesions. The effect of hippocampal lesions on performance in two psychophysical measures of spatial vision (acuity and size-difference threshold) was examined in 7 pigeons. No difference between the preoperative and postoperative thresholds of the experimental birds was found. The visual performance of pigeons in the psychophysical tasks failed to reveal a role of the hippocampal formation in vision. The results argue strongly that the behavioral deficits found in pigeons with hippocampal lesions when tested in a variety of memory-related spatial tasks is not based on a defect in spatial vision but impaired spatial cognition.


Visual discrimination performance after lesions of the ventral lateral geniculate nucleus in pigeons (Columba livia). Pigeons were trained to perform simultaneous pattern and color discrimination tasks. After their training was completed, bilateral electrolytic lesions were made in the ventral lateral geniculate nucleus (GLv). Following the surgery, they were retrained to their preoperative performance levels. Lesions of GLv caused no deficits in pattern discrimination performance. The birds which had been trained for discrimination of red vs. magenta showed a slight decline in their performance. This impaired performance on color discrimination was not, however, as severe as that of a bird with lesions in the nucleus rotundus. These results suggest that GLv plays some role in the detection of short wavelengths of light.


Descending pathways and the hopping response in the rabbit. Descending pathways were studied in 5 adult rabbits by means of HRP, injected in the cervical spinal cord (in C2 and C3) at the right side. Results indicate the existence of pathways from the contralateral motor cortex, bilateral projections from the red nuclei, from the vestibular nuclei and from several nuclei in the reticular formation.


Inhibition of myosin light chain kinase, cAMP-dependent protein kinase, protein kinase C and of plant Ca(2+)-dependent protein kinase by anthraquinones. A variety of anthraquinone (anthracene-9,10-dione) derivatives inhibits rat brain Ca(2+)- and phospholipid-activated protein kinase C (PKC) of which the most potent inhibitors are mitoxantrone (1,4-dihydroxy-5,8-bis[2-(hydroxyethylamino)-ethylamino]-9,10- anthracenedione) (IC50 4 microM) and quinalizarin (1,2,5,8-tetrahydroxy-anthraquinone (IC50 4 microM). Anthraquinone derivatives with less polar substitution in positions 1 to 4 and 5 to 8 are less effective as inhibitors of PKC. Wheat germ Ca(2+)-dependent protein kinase (CDPK) assayed with a myosin light chain-based peptide substrate is much less sensitive to inhibition by anthraquinones, the most effective anthraquinone inhibitors being the 1,2,4-trihydroxy (IC50 14 microM), 1,8-dihydroxy-3-methyl (IC50 56 microM) and 1,2,5,8-tetrahydroxy (IC50 65 microM) derivatives. Ca(2+)-calmodulin-dependent myosin light chain kinase (MLCK) is inhibited by a range of di-, tri- and tetrahydroxylated anthraquinones (IC50 values 2 to 53 microM), the most potent inhibitors being the more polar compounds, namely mitoxantrone (IC50 2 microM) and emodin (1,3,8-trihydroxy-6-methylanthraquinone) (IC50 8 microM). Mitoxantrone interacts with calmodulin as determined from abolition of Ca(2+)-dependent fluorescence enhancement of dansyl-calmodulin (IC50 4 microM). A range of anthraquinone derivatives inhibits the catalytic subunit of cAMP-dependent protein kinase (cAK). In a number of cases compounds acting as potent inhibitors of MLCK (such as mitoxantrone and emodin) are very poor inhibitors of cAK and vice versa.


Analysis of the human insulin receptor.

Analysis of the human insulin receptor. The insulin derivative 4-azidosalicyloyl-[B1-biocytin-B2-lysine]insulin was used to photo-affinity-label the highly purified insulin receptor from human placenta. As shown by SDS-polyacrylamide gel electrophoresis, the 5 monoiodo isomers, with iodine in positions B1, B16, B26, A14 or A19, gave different labelling patterns. After complete tryptic digestion of the covalent receptor complex with 125I-Asa-[BctB1,LysB2]insulin, a stable fragment of 18 kDa was isolated, which was further purified by HPLC. This tryptic fragment of the intact receptor corresponds, according to HPLC, Tricin-SDS-PAGE and 2D-electrophoresis, to the similarly labelled sequenced domain of the receptor ectodomain (Fabry, M. et al. (1992) J. Biol. Chem. 267, 8950-8956). We thus conclude that insulin is bound to identical contact sites of native receptor and truncated ectodomain.


3-Hydroxy-3-methylglutaryl-CoA reductase mediates the preparation of its substrate diastereomers and is inhibited by (3R)-3-hydroxy-3-methylglutaryl-CoA. Stereochemically pure samples of enzymically active (3S)-3-hydroxy-3-methylglutaryl-CoA and its enzymically inactive R diastereomer were prepared in good yield with a genetically engineered catalytic fragment of human 3-hydroxy-3-methylglutaryl-CoA reductase. The inhibitory properties of the R stereoisomer were determined in reactions with 3S and 3RS substrate and were shown to be of partially competitive type. Ki values of competitive inhibitors are shown to be approximately equal if determined with either stereochemically pure substrate or the diastereomeric 3RS mixture containing the inhibitory stereoisomer.


The amino-acid sequence of two isoforms of alpha-lactalbumin from donkey (Equus asinus) milk is identical. The complete primary structure of donkey alpha-lactalbumin A and B has been determined by sequencing of the peptides obtained after tryptic, Glu-C proteinase or cyanogen bromide cleavage. Although preparative purification of alpha-lactalbumin by flat-bed isoelectric focusing gave two protein fractions A and B, their amino-acid sequence revealed no differences. Donkey alpha-lactalbumin shows two, four and five differences in comparison to the horse alpha-lactalbumin A, B and C. Thus donkey alpha-lactalbumin is homogeneous and belongs to the horse A-type variant.


The primary structure of the hemoglobin from the tomb bat (Taphozous georgianus, Microchiroptera). The primary structures of the alpha- and beta-chains of the single hemoglobin component from the tomb bat (Taphozous georgianus, Microchiroptera) are presented. After chain separation by reversed-phase HPLC the sequences could be determined by automatic gas and liquid phase Edman degradation of the chains and their tryptic peptides. The alpha- and beta-chains differ from human hemoglobin by 14 and 18 replacements, respectively. Compared to the total number of amino-acid exchanges, the exchange rate in the interhelical regions of the alpha-chains is surprisingly high (25%). It seems unlikely that substitutions at contact positions affect the oxygen binding properties of the hemoglobin.


T-cell tolerance.

T-cell tolerance. Despite the acceptance of principles such as clonal deletion in the thymus and peripheral clonal anergy, several new issues have arisen in the study of T-cell tolerance. For example, in the case of thymic tolerance, it is now clear that several distinct components of the thymus, including various subsets of thymic epithelial cells, can all make contributions to the deletion of autoreactive T cells. In the case of peripheral T-cell tolerance, the induction of anergy now has been complicated by the possibility that bone marrow derived antigen presenting cells may, under certain conditions, be tolerogenic rather than stimulatory.


Transgenes in autoimmunity.

Transgenes in autoimmunity. The ability of transgenic mice to express a specific protein in a specific tissue has enabled the mechanisms of self-tolerance and autoimmunity to be elucidated. Further studies, combined with more sophisticated methods of gene targeting, will provide insights into the pathway leading from loss of self-tolerance to autoimmunity.


T-cell subsets in autoimmunity.

T-cell subsets in autoimmunity. The demonstration that functionally different T-cell subsets can be defined by the isoforms of the leukocyte-common antigen, CD45, that they express, has prompted studies on the roles of these subsets in autoimmunity. The results have led to the identification of a particular subset of CD4+ T cells that have the ability to inhibit autoimmune disease. Further, it has been shown that diabetes in the B-B rat can be transferred by in vitro activation of T cells by Staphylococcal enterotoxin suggesting that superantigens may play a role in the pathogenesis of this disease. However, in this system too, it appears that a subset of T cells can inhibit the induction of autoaggressive cells. In other experimental autoimmune diseases there is evidence that CD8+ T cells can be protective and that these cells may mediate this protection by the synthesis of transforming growth factor-beta.


B-cell responses in autoimmune diseases. Autoantibodies are detected in most autoimmune diseases. Beyond their direct role in mediating tissue damage in some models, the characterization of several intracellular autoantigens and the study of the autoimmune B-cell repertoire favor an antigen-driven B-cell response in most autoimmune models studied.


Peptide-MHC interaction in autoimmunity. Our increased understanding of the molecular basis of autoimmunity owes much to an appreciation of general principles governing peptide-MHC interactions. Such understanding may help resolve long-standing questions concerning autoimmune diseases and aid development of improved therapeutic strategies for their treatment.


Cytokines in autoimmunity.

Cytokines in autoimmunity. It is now generally accepted that many cytokines are involved in the pathogenesis of autoimmune disease, either directly by causing tissue destruction or indirectly through the activation of autoreactive and inflammatory cells. Thus, cytokines, such as tumor necrosis factor-alpha, are implicated in the pathogenesis of rheumatoid arthritis based on in vitro studies on synovial tissue from patients with rheumatoid arthritis, which suggest that the effects of tumor necrosis factor-alpha are amplified by its potential to induce other pro-inflammatory cytokines, such as interleukin-1 and granulocyte-macrophage colony-stimulating factor. Transgenic mouse technology has shown that mice expressing the human tumor necrosis factor-alpha gene develop a polyarthritis. Interleukin-2 has also been identified by transgenic technology as a cytokine involved in the pathogenesis of insulin-dependent diabetes mellitus through the activation and stimulation of growth of autoreactive T cells.


Rheumatoid arthritis.

Rheumatoid arthritis. Rheumatoid arthritis is often considered to be an autoimmune disease in which the abnormal immunological response is triggered by an infectious agent(s) but progress towards identifying such extrinsic factors has so far been unrevealing. In contrast, the genetic component of host susceptibility is slowly becoming clearer. In particular, the nature of the HLA class II association with the disease has led to new insights into its pathogenesis and possible novel forms of therapy.


Thyroid autoimmunity.

Thyroid autoimmunity. Antigenic structure remains a major focus in thyroid immunology. The genes for three major thyroid antigens--thyroglobulin, thyroid peroxidase and the thyrotropin receptor--were sequenced in the late 1980's, and epitopes for antibody and T cells have been reported within the last year. In addition, new evidence for selective use of T-cell receptor V gene segments in human thyroid infiltrates may point the way to specific immunotherapy.


Roles of eosinophils in allergy.

Roles of eosinophils in allergy. In the past year insights have been gained into mechanisms whereby eosinophils are mobilized from the vasculature to enter sites of inflammation. In addition, the responses of eosinophils to specific cytokines have been delineated. Moreover, for the first time it has become clear that eosinophils themselves are sources of cytokines that may exert not only autocrine effects on eosinophils but also paracrine effects on adjacent cells within tissues.


Role of type 1 and type 2 T helper cells in allergic diseases. Various characteristics of atopic allergic disorders seem to be causally related with the activation of allergen-specific T helper lymphocytes with a type 2 cytokine secretion profile, including high levels of interleukin-4 and interleukin-5. These cytokines are responsible for the occurrence of elevated levels of serum allergen-specific IgE and eosinophilia and play an important role in local inflammatory reactions.


Regulation of isotype switching.

Regulation of isotype switching. In the past year, our understanding of the mechanisms that regulate isotype switching has significantly progressed. Activation of germ line transcription by isotype-specific cytokines is emerging as a crucial mechanism for increasing the accessibility of a particular switch region, and targeting switch recombination.


Allergy of the respiratory tract.

Allergy of the respiratory tract. The past year has seen significant advances in several fields of asthma and allergy research. Notable among these advances were the following: the demonstration that inflammatory granulocytes may be a source of cytokines; an increased understanding of the inter-relationships between the inflammatory cells invading the asthmatic bronchial mucosa; some important new approaches to asthma therapy; and the beginnings of a systematic classification of the structure of allergens and their antigenic epitopes.


Conformational effects of selected cancer-related amino acid substitutions in the p53 protein. The tumor suppressor gene p53 has been identified as the most frequent target of genetic alterations in human cancers. Cancer-related mutations in the human p53 protein tend to cluster in four of the five highly conserved domains of the protein, and, in particular, in the central region of domain IV from residues 241 to 253. Using conformational energy analysis based on ECEPP (Empirical Conformational Energies for Polypeptides Program), we have determined the preferred three dimensional structures for this tridecapeptide sequence for the human wild-type p53 protein and four cancer-related mutant p53 proteins (Ala 245, Ile 246, Trp 248, Ser 249). The results show that the mutant peptides adopt conformations that are distinctly different from that of the wild-type peptide. These results are consistent with experimental conformational studies demonstrating altered detectability of antigenic epitopes in murine wild-type and mutant p53 proteins. These results suggest that the oncogenic effects of human mutant p53 proteins may be mediated by distinct local conformational changes in the protein.


Comparison of protein models minimized by the all-atom and united-atom models in the AMBER force field: correlation of RMS deviation with the crystallographic R factor and size. We performed energy minimization of 25 protein structures, which vary significantly in their size, secondary structural content and crystallographic R factor, in the AMBER force field. We used an unconstrained path and the conjugate gradients algorithm. To determine the reliability of the united-atom approximation, we minimized all the proteins using both the all-atom and united-atom models. The RMS deviations of the minimized structures were plotted as a function of the crystallographic R factors of the initial structures. For the all-atom models, we found a strong linear relationship between the RMS deviations and the R factors (correlation coefficient of 0.78). The RMS deviations of protein structures minimized using united-atom models showed a wider range of distribution and had a correlation coefficient with the R factors of only 0.52. The RMS deviations decrease with an increase in the size of the protein, probably due to the decreased ratio of surface area to volume with increasing size of the protein. The surface atoms and residues showed higher RMS deviations than those in the interior of the protein. Even in these plots the united-atom models show a wide range of distribution of data points. From these results, we recommend the use of all-atom models for energy minimization of proteins in the AMBER force field.


Structural aspects of Ca2+ binding by acyclic peptides: low-energy conformational domains and molecular dynamics of N-acetyl-L-prolyl-D-alanyl-L-alanine-N'-methylamide. We have applied random-search, energy minimization and molecular dynamics simulations to investigate the structural aspects of the interaction of N-acetyl-L-prolyl-D-alanyl-L-alanine-N'-methylamide with Ca2+. Spectral data on related peptides had suggested that the beta-turn conformation might be a prerequisite for the binding of cation ion by such short linear peptides. In order to relate the conformational characteristics with the Ca(2+)-binding affinities of these peptides, the molecular events involved in cation binding need to be understood. We have addressed this problem in this study by using a systematic approach that involved the following steps. First, a random search technique was used to generate a large population of conformers for the free peptide in the absence of Ca2+. Next, the energies of these conformers were computed. Conformations with energies within 4 kcal/mol of the global minimum were analysed and found to fall into four main groups characterized by the presence of different types of hydrogen-bonded structures including single and consecutive beta-turns. The energies for interconversion of conformers from one group to another were computed and found to be relatively small (< 10 kcal/mol). Finally, molecular dynamics of the peptide at 300K in the presence of Ca2+ were used to simulate the cation binding process. Starting points for these simulations were generated by placing the ion in the vicinity of two molecules of the peptide. The simulation results showed that the conformers with two consecutive beta-turns led to the formation of a stable 2:1 (peptide:Ca2+) sandwich complex in agreement with earlier experimental observations on similar linear peptides. While the starting conformation of the peptide in the consecutive beta-turn structure allowed for the proper orientation of three carbonyl oxygen atoms for chelation to the metal ion, the dynamics of complex formation rearranged the peptide structure substantially, leading to the formation of an 8-coordinated Ca2+ complex in a dodecahedral spatial arrangement. Thus, based on the energetics of the structures and processes involved, the present study demonstrates that: a) peptide-Ca2+ complex formation is initiated by conformers adopting consecutive beta-turn structures which subsequently go over to a significantly different conformation found in the complex; and, b) The facile interconversion between the low-energy conformers in the different groups would help shift the equilibrium population towards the consecutive beta-turn structure during the complex formation.


Binding of DNA to large fragment of DNA polymerase I: identification of strong and weak electrostatic forces and their biological implications. Examination of the electrostatic potential of a modeled complex, consisting of the Klenow fragment of E. coli DNA polymerase I and DNA template-primer, suggested the presence of two distinct interacting regions. The one displaying a strong electropositive potential field is generated by side chains of basic amino acid pairs and is directed towards the major groove site in DNA. The second electrostatic potential field around DNA is somewhat weaker and appears to be exerted by a pair of vicinal side chains of acidic and basic amino acids. The distribution of charges in this manner appears well suited for the binding of enzyme to the template-primer required in the enzymatic synthesis of DNA.


A structural model for sequence-specific proflavin-DNA interactions during in vitro frameshift mutagenesis. Molecular models describing intermediates that may lead to proflavin-induced 1 bp deletions during in vitro polymerization by E. coli DNA polymerase I Klenow fragment are proposed. The models provide structural explanations for the fact that the induced frameshifts always occur opposite template bases that are adjacent to 5' pyrimidines and are based on the underlying hypothesis that the deletions arise because the polymerase passes by a template base without copying it. Because the most frequent mutations are opposite Pu in the template sequence 5' Py Pu 3', a single-strand loop-out model was constructed for this sequence and proflavin was added, using structures found in crystalline oligonucleotides and their complexes with proflavin. The model seeks to rationalize the roles of the 5' pyrimidine and proflavin in facilitating the bypass. Four potential roles for proflavin in mutagenesis are described: 1) stacking on the looped-out base; 2) stacking on the base pair immediately preceding the site of mutation; 3) hydrogen bonding with the 5' pyrimidine; 4) hydrogen bonding with the phosphate backbone. These models point to the possibility that a number of proflavin-DNA interactions may be involved. In contrast, modeling does not suggest a role for classically intercalated proflavin in frameshift mutagenesis arising during in vitro DNA polymerization.


Ca2+ binding environments on natural and synthetic polymeric DNA's. Here are reported 43Ca nmr chemical shift and line width measurements obtained during 43CaClO4 titrations of two natural and two synthetic polymeric DNA's. Titrations of the natural DNA's demonstrate the existence of at least two classes of bound 43Ca2+. The 43Ca2+ nmr relaxation and chemical shift behavior observed during titration of C. perfringens DNA (31%GC) is dominated by a delocalized, non-specific interaction. In contrast, titration of M. lysodeikticus DNA (72% GC) indicates that a small fraction of the 43Ca2+ experiences significant motional retardation and/or an increase in the electric field gradient when associated to the DNA, and thus appears to be locally bound to discrete sites on the DNA. These results, and previous results for calf thymus DNA (39% GC) demonstrate that higher GC content correlates with an increase in favorable Ca2+ binding environments. Titrations of synthetic DNA demonstrate that Ca2+ binding is remarkably sensitive to local DNA structure.


A molecular mechanics investigation of RNA complexes. I. Ethidium intercalation in an HIV-1 TAR RNA sequence with an unpaired adenosine. Nucleic acid complexes with ethidium intercalated into different sites in a segment of HIV-1 TAR RNA with an unpaired A base, along with corresponding complexes with a normal RNA sequence without an unpaired base were studied by molecular mechanics energy minimization methods. Different intercalation geometries as well as different orientations of the ethidium molecule in the intercalation sites were tested. A general binding affinity enhancement for the ethidium binding to the bulge sequence compared with the normal RNA segment was obtained. With the unpaired adenosine base stacked in the duplex, the binding site adjacent to the 3' side of the bulge was found to be the most energetically favorable binding site, and the intercalation site 5' to the bulge in the same sequence is much less favorable. Unique correlated backbone conformational changes on binding of ethidium to the intercalation site 3' to the bulge were found to relieve backbone strains caused by the stacking of the unpaired base into the helix. These backbone conformational changes present a plausible molecular basis for the experimentally observed ethidium binding preference in this bulge RNA segment (L.S. Ratmeyer, R. Vinayak, G. Zon and W.D. Wilson, J. Med. Chem. 35, 966, 1992).


The interface between an alternating CG motif and a random sequence motif displays altered nuclease activity. Previously we described the B-Z junctions produced in oligomers containing (5meCG)4 segments in the presence of 5.0 M NaCl or 50 uM Co(NH3)6+3 [Sheardy, R.D. & Winkle, S.A., Biochemistry 28, 720-725 (1989); Winkle, S.A., Aloyo, M.C., Morales, N., Zambrano, T.Y. & Sheardy, R.D., Biochemistry 30, 10601-10606 (1991)]. The circular dichroism spectra of an analogous unmethylated oligomer containing (CG)4, termed BZ-IV, in 5.0 M NaCl and in 50 uM Co(NH3)+3 suggest, however, that this oligomer does not form a B-Z hybrid. BZ-IV possesses Hha I sites (CGCG) in the (CG)4 segment and an Mbo I site (GATC) at the terminus of the (CG)4 segment. BZ-IV is equally digestible in the presence and absence of cobalt hexamine by Hha I, further indicating that the structure of BZ-IV is fully B-like under these conditions. The Mbo I cleavage site at the juncture between the (CG)4 segment and the adjacent random segment displays enhanced cleavage by both Mbo I and its isoschizomer Sau3AI in the presence of cobalt hexamine. In addition, exonuclease III digestion of BZ-IV is inhibited at this juncture. Actinomycin inhibits Mbo I activity in the presence of cobalt hexamine but not in the absence. Together, these results suggest that enzymes recognize the interfaces of (CG)n and adjacent random sequences as altered substrates even in the absence of a B-Z junction formation.


Description of base motion and role of excitations in the melting of poly(dG).poly(dC). We study the contribution of various vibrational modes to the melting of poly(dG).poly(dC). We find that the principal contribution comes from the H-bond breathing modes that have been observed in Raman scattering and that we have associated with helix melting. We show the softening of these modes on approach to melting in agreement with the observed behavior. We also describe the contribution to melting from base rotation modes that others have suggested are important in melting.


Energy flow considerations and thermal fluctuational opening of DNA base pairs at a replicating fork: unwinding consistent with observed replication rates. The effect of an open loop of various sizes on the thermal stability of the adjoining intact base pairs in a duplex DNA chain is studied in a lattice model of Poly(dG).Poly(dC). We find that for a Y-shaped fork configuration the thermal fluctuation at the fork is so enhanced that the life time of the adjoining base pair is much smaller than the 1 millisecond time scale associated with helicase separation of a base pair in some systems. Our analysis indicates that thermal fluctuational base pair opening may be of importance in facilitating the enzyme unwinding process during chain elongation of a replicating DNA. It is most likely that the thermal fluctuational opening of the base pair at the junction of a replicating fork is fast enough so that a DNA unwinding enzyme can encounter an unstacked base pair with reasonable probability. This conclusion can explain several experimental observations regarding the temporal relationship between ATP hydrolysis by accessory proteins and primer elongation by a holoenzyme complex in ssDNA. We also discuss a mechanism by which the energy associated with ATP hydrolysis may enhance the thermal driven base opening mechanism.


Age-related differences in concurrent-task performance of normal adults: evidence for a decline in processing resources. A concurrent-task paradigm was used to investigate age-related differences in the attentional capacity of 92 right-handed adults. Young, middle-aged, and elderly Ss were compared as they performed speeded, unimanual finger tapping with and without concurrent silent reading, speaking, and maze completion. There were 2 levels of difficulty for each cognitive task. The decrement in tapping rate from the single- to dual-task condition increased linearly with age. Concurrent-task tapping was slowed more by difficult than by easy tasks, and difficult tasks had a disproportionately disruptive effect on the concurrent performance of elderly Ss. The heightened vulnerability of the elderly to concurrent-task effects cannot be attributed parsimoniously to either general slowing or diminution of a specific resource. Instead the results suggest a reduction in a general-purpose processing resource with increasing age.


The interpretation of life experience and well-being: the sample case of relocation. Social psychological theories of the self postulate mechanisms through which individuals interpret their life experiences to ensure positive self-evaluation. This framework was applied to a sample of aging women (N = 120, M age = 74.9 years) who had experienced community relocation. The authors measured their reasons for moving (push factors), reasons for selecting the new setting, (pull factors), and interpretive mechanisms, including how they compared with others in their new setting, how they were viewed by significant others following the move, how their behaviors changed following relocation, and whether the above evaluations occurred in life domains central to their sense of self. Regression analyses showed that push-pull factors and interpretive mechanisms accounted for substantial variance in multiple aspects of psychological well-being, particularly environmental mastery, purpose in life, and positive relations with others.


Aging persons' estimates of vehicular motion. Estimated arrival times of moving autos were examined in relation to viewer age, gender, motion trajectory, and velocity. Direct push-button judgments were compared with verbal estimates derived from velocity and distance, which were based on assumptions that perceivers compute arrival time from perceived distance and velocity. Experiment 1 showed that direct estimates of younger Ss were most accurate. Older women made the shortest (highly cautious) estimates of when cars would arrive. Verbal estimates were much lower than direct estimates, with little correlation between them. Experiment 2 extended target distances and velocities of targets, with the results replicating the main findings of Experiment 1. Judgment accuracy increased with target velocity, and verbal estimates were again poorer estimates of arrival time than direct ones, with different patterns of findings. Using verbal estimates to approximate judgments in traffic situations appears questionable.


Age differences in visual search: target and distractor learning. Age differences in a semantic category visual search task were investigated to determine whether the age effects were due to target learning deficits, distractor learning deficits, or a combination thereof. Twelve young (mean age 20) and 12 older (mean age 70) adults received 2,400 trials each in consistent and varied versions of the search task. Following training, a series of transfer-reversal manipulations allowed the assessment of target learning and distractor learning both in isolation and in combination. The pattern of data suggests that older adults have a deficit in their ability to increase the attention-attraction strength of targets and to decrease the attention-attraction strength of distractors. The results are interpreted in terms of a strength-based framework of visual search performance.


On mental multiplication and age.

On mental multiplication and age. In 2 experiments, younger and older adults were presented with simple multiplication problems (e.g., 4 x 7 = 28 and 5 x 3 = 10) for their timed, true or false judgments. All of the effects typically obtained in basic research on mental arithmetic were obtained, that is, reaction time (a) increased with the size of the problem, (b) was slowed for answers deviating only a small amount from the correct value, and (c) was slowed when related (e.g., 7 x 4 = 21) versus unrelated (e.g., 7 x 4 = 18) answers were presented. Older adults were slower in their judgments. Most important, age did not interact significantly with problem size or split size. The authors suggest that elderly adults' central processes, such as memory retrieval and decision making, did not demonstrate the typical age deficit because of the skilled nature of these processes in simple arithmetic.


Rapid speech processing and divided attention: processing rate versus processing resources as an explanation of age effects. The authors conducted a dual-task study to examine age differences in speech processing under varying loads. Younger and older adults listened to and immediately recalled spoken passages presented at various speech rates (140-280 words per min). This task was performed alone as well as in a divided-attention condition in which subjects concurrently performed a picture recognition task. Consistent with the slowing hypothesis, older adults' immediate memory performance was differentially depressed when speech rates were very fast. The Age x Speech Rate interaction, however, was not exacerbated in the divided-attention condition. This suggests that aging may reduce the rate at which the processing operations underlying memory for speech are completed, but this is conceptually distinct from an age-related reduction in attentional capacity.


Type A behavior pattern and emotion expression in younger and older adults. Eighty younger (less than 50 years, M = 28 years) and 80 older (more than 50 years, M = 69 years) Type A and Type B Ss were evaluated for Type A behavior pattern using the Structured Interview (SI) and given personality tests for anxiety, depression, anger, aggression, hostility, and anger-in-anger-out. Ss also underwent an emotion induction procedure. Videotapes of the emotion induction procedure (N = 160) and the SI (N = 80) were coded for facial expression of emotion. Type As did not differ from Bs on anxiety or depression but did on anger and aggression. Type As showed anger inhibition and anger bound to shame, as predicted by emotion socialization theory. The greatest number of differential effects were observed between age groups. Older individuals, in general, were more emotionally expressive than younger Ss across a range of emotions. Women appeared more conflicted about anger expression than men, and Type A women more so than Type A men.


Functional versus structural social support, desirable events, and positive affect in older adults. The independent contributions of structural social support versus functional support to positive affect in older adults were compared in this prospective design. Four social support models were translated from the stress-symptoms literature into promotional models for positive mental health and for relationships to desirable challenge events. A total of 1,031 older adults were interviewed 5 times at 6-month intervals, and events were measured across the middle 18-month period. The 2 support variables made quite different contributions. Functional support was directly related to positive affect 2 years later, independent of events; structural support had more transitory direct effects. Structural support, but not functional support, was related to the subsequent occurrence of challenge events and in turn was strengthened by challenge events, suggesting a dynamic interplay between the social network and desirable events.


Short-term longitudinal change in cognitive performance in later life. Changes in mean performance on memory, information processing, and intellectual ability tasks over a 3-year period were examined. The sample consisted of 328 community-dwelling men and women (from an original sample of 484 individuals) aged 55-86 years. Ss completed tasks yielding measures of verbal processing time, working memory, implicit memory, vocabulary, verbal fluency, world knowledge, reading comprehension, word recall, and text recall. The results showed significant average decline on working memory, verbal fluency, and world knowledge. There were also interactions for 2 processing time measures and working memory, showing greater decline in the earlier-born cohort group than in the later-born cohort group. A step-down analysis revealed that covarying declines in other variables, including processing time, did not eliminate significant declines in working memory, verbal fluency, and world knowledge.


Professional expertise does not eliminate age differences in imagery-based memory performance during adulthood. Using a testing-the-limits paradigm, the authors investigated the modulation (attenuation) of negative adult age differences in imagery-based memory performance as a function of professional expertise. Six older graphic designers, 6 normal older adults, 6 younger graphic design students, and 6 normal younger students participated in a 19-session program with a cued-recall variant of the Method of Loci. Older graphic designers attained higher levels of mnemonic performance than normal older adults but were not able to reach younger adults' level of performance; a perfect separation of age groups was achieved. Spatial visualization was a good predictor of mnemonic performance. Results suggest that negative adult age differences in imagery-based memory are attenuated but not eliminated by the advantages associated with criterion-relevant ability (talent) and experience.


Adult age differences in attentional allocation during memory search. Young and older adults performed a memory search task in which, before probe onset, a cue indicated which of 4 memory-set items the probe was most likely to be. The results were consistent with an attentional allocation model in which performance represents a weighted combination, across trials, of focused (i.e., selective) versus distributed attention. The model significantly underestimated the reaction time required by miscued trials, probably because of the response inhibition occurring on these trials. The degree to which Ss relied on focused attention was significantly greater for older adults than for young adults. The estimated time required to shift attention between memory-set items was equivalent for the 2 age groups.


Eyewitness memory and aging: predictors of accuracy in recall and person recognition. This study examined adult age differences in identification accuracy, confidence, and verbal recall of crime films. A total of 120 Ss in 3 adult age groups watched 2 crime films that contained characters varying in role and visibility. Results suggested a modest negative relationship between age and identification accuracy but no age differences in recall of main points or details. Education and self-reported health positively predicted verbal recall, but higher education was associated with lower identification accuracy. No age differences were found in confidence or in the relationship between confidence and accuracy.


Assessing retirement satisfaction and perceptions of retirement experiences. A 2-part investigation developed a measure of retirement as a life transition. Study 1 generated items from interviews with retirees (n = 40) and service providers. Item analysis with recent retirees (n = 86) produced a 51-item Retirement Satisfaction Inventory assessing 6 areas: preretirement work functioning, adjustment and change, reasons for retirement, satisfaction with life in retirement, current sources of enjoyment, and leisure and physical activities. Study 2 examined a heterogeneous sample of men (n = 159) and women (n = 243) retires. Factor analyses produced internally consistent subscales. Moderate, but acceptable, test-retest reliability was demonstrated. Satisfaction scores correlated with concurrent measures and, together with pre- and postretirement experiences, discriminated 4 groups of voluntary and involuntary retirees. Few effects related to gender, socioeconomic status, length of retirement, and part-time employment were found.


Assessment of behavioral problems in dementia: the revised memory and behavior problems checklist. The Revised Memory and Behavior Problems Checklist (RMBPC), a 24-item, caregiver-report measure of observable behavioral problems in dementia patients, provides 1 total score and 3 subscale scores for patient problems (memory-related, depression, and disruptive behaviors) and parallel scores for caregiver reaction. Data were obtained from 201 geriatric patients and their caregivers. Factor analysis confirmed 3 first-order factors, consistent with subscales just named, and 1 general factor of behavioral disturbance. Overall scale reliability was good, with alphas of .84 for patient behavior and .90 for caregiver reaction. Subscale alphas ranged from .67 to .89. Validity was confirmed through comparison of RMBPC scores with well-established indexes of depression, cognitive impairment, and caregiver burden. The RMBPC is recommended as a reliable and valid tool for the clinical and empirical assessment of behavior problems in dementia patients.


Effect of environmental support on implicit and explicit memory in younger and older adults. The study addressed 2 major issues: whether there are age differences on an implicit word-stem-completion task and whether age differences on both implicit and explicit memory would decrease with increased environmental support. A total of 287 Ss were presented with words in an incidental learning task with structural or semantic processing. Following 2 filler tasks, Ss received an implicit or an explicit word-stem-completion task. The number of letters in the stem varied from 2 to 4. Results yielded an Age x Memory Task dissociation such that there were large age differences on the explicit task and no age difference on the implicit task, regardless of whether Ss aware of the memory test were included or excluded. There was no evidence that environmental support improved older adults' performance more than that of younger adults on either memory task.


Aging, exercise, and attention.

Aging, exercise, and attention. The authors investigated the relationship among aging, attentional processes, and exercise in 2 experiments. First they examined age differences on 2 attentional tasks, a time-sharing task and an attentional flexibility task. Young adults alternated attention between 2 sequenced tasks more rapidly and time-shared the processing of 2 tasks more efficiently than older adults. They then investigated the effects of aerobic exercise on the same 2 attentional tasks in older adults. Following the 10-week exercise program, older exercisers showed substantially more improvement in alternation speed and time-sharing efficiency than older controls. Interestingly, this exercise effect was specific to dual-task processing. Both groups of subjects showed equivalent effects on single-task performance. These results indicate that aerobic exercise can exert a beneficial influence on the efficiency of at least 2 different attentional processes in older adults.


Motion perception and aging.

Motion perception and aging. The authors used a correlated motion paradigm to investigate the effects of aging and gender on motion sensitivity. In 2 experiments with a total of 50 elderly and 50 young subjects, motion thresholds were significantly higher for elderly women. The correlated motion signal, which was embedded in random motion, may have been coherent to subjects in much the same way a form is in Witkin's Embedded Figures Test (EFT). In Experiment 2, EFT scores were obtained. A significant positive relationship between motion thresholds and EFT performance was found within each age group. Although gender-related perceptual style differences may contribute to motion perception effects, the authors argue that a common neural factor contributes to performance on both the EFT and the correlated motion task.


Age-related differences in three tests of visual imagery. Adult age differences were explored on 3 short tests of the ability to generate and manipulate mental images. Age-related decrements were found in all 3 tests and were especially marked on the Clock Test. The tests are all reliable, as shown by test-retest reliability coefficients. Correlations also revealed that the Brooks Letter Test and the East-West Test appear to tap one common underlying ability, whereas the Clock Test measured a somewhat different ability. The East-West and Clock tests, in particular, may provide rapid and easily administered assessments of age-related changes in aspects of mental imagery.


Use of physical chemistry and in vivo exposure to investigate the toxicity of formaldehyde bound to carbonaceous particles in the murine lung. Knowledge about the health effects of exposure to formaldehyde associated with automotive emissions is of pivotal importance in the risk assessment of this agent. Mobile sources emit many combustion-derived pollutants, including formaldehyde, in association with respirable carbon particles. Because it is hydrophilic, most of the inhaled formaldehyde is absorbed in the upper respiratory tract. However, if the organic vapor is adsorbed on respirable particles, formaldehyde may be deposited in the deep lung with the inhaled particles and may be available to interact adversely with cells along the lung parenchyma. On the respiratory surface, the alveolar macrophage phagocytic system plays the pivotal role in defending the lung against infectious agents. Susceptibility to respiratory infections is a relevant and sensitive indicator of the adverse effects of air pollution because acute and chronic exposures to a variety of air pollutants have been shown to decrease pulmonary antibacterial defenses. The goal of this research was to investigate whether exposure to formaldehyde decreases resistance to respiratory infections through dysfunctions of the alveolar macrophage phagocytic system. The study also explored whether interactions between formaldehyde and respirable carbon black particles alter susceptibility to respiratory infections and impairment of alveolar macrophage phagocytosis by delivering adsorbed formaldehyde to the deep lung with the inhaled particles. A carbon black, Regal GR, was used in these studies as a surrogate for the carbonaceous core of Diesel particulate matter. This material was selected to represent the worst-case scenario because the carbon black was expected to adsorb formaldehyde strongly. To accomplish this goal, mice were exposed to formaldehyde and to carbon black and formaldehyde combinations; increased susceptibility to respiratory infections was quantified by alveolar macrophage-dependent intrapulmonary killing of Staphylococcus aureus after an inhalation challenge with the bacterium. The salient findings of the bactericidal studies are as follows: Fifteen parts per million (ppm)* formaldehyde impaired the intrapulmonary killing of S. aureus when exposure followed the bacterial challenge. One ppm formaldehyde impaired the intrapulmonary killing of S. aureus when exposure preceded and was continued after the bacterial challenge. Coexposures to target concentrations of 3.5 mg/m3 carbon black and 2.5 ppm formaldehyde, or 10 mg/m3 carbon black and 5 ppm formaldehyde after the bacterial challenge had no effect on the intrapulmonary killing of S. aureus. Preexposure for four hours per day for four days to target concentrations of 3.5 mg/m3 carbon black and 2.5 ppm formaldehyde had no effect on the intrapulmonary killing of S. aureus when the assay was performed one day after the cessation of exposure.(ABSTRACT TRUNCATED AT 400 WORDS)


The induction of cataracts by HIV-1 in transgenic mice. To elucidate the tissue specificity of the expression of HIV-1 genes in an animal and its pathological effects on these tissues. Transgenic mice carrying a defective HIV-1 genome were bred in order to overcome the host-range barrier of this virus. mRNA specific to the transgene was detected in the eyes and the spleen, and, in smaller quantities, in the thymus and the brain. Interestingly, many of the transgenic mice developed cataracts at 3-6 months of age. Swelling and vacuolation of the lens fiber cells were marked, but the epithelial cells of the lens were less affected. HIV antigens were detected in the lens fiber cells and the retina by immunological staining. Accumulation of large amounts of p24 Gag antigen was demonstrated in the affected lens by immunoblot analysis, while negligible Env or other viral proteins was detected. Although accumulation of the Gag protein was also detected in the skin and the brain, no apparent abnormality was observed in these tissues. Preferential expression of the HIV genes in the eyes, skin, brain and lymphoid tissues was demonstrated. The accumulation of the Gag protein is suggested to have detrimental effects on lens fiber cells, causing cataracts.


Virus-specific cytotoxic T-lymphocytes in HIV-2-infected cynomolgus macaques. Specific cytotoxic T-lymphocytes (CTL) are induced in humans or monkeys after infection with HIV-1 or SIVmac, respectively. Since, like HIV-1, HIV-2 causes AIDS, our objective was to determine the characteristics of the HIV-2-specific CTL response. Since it is rarely possible to study cellular immunity in individuals, because of the small number of HIV-2-infected patients available in Europe and the necessity for co-operation in the performance of sequential CTL assays, cynomolgus macaques were infected with HIV-2. Autologous transformed B-lymphoblastoid cell lines infected with recombinant vaccinia viruses were used as target cells for cytotoxicity assays. Recombinant vaccinia viruses expressing HIV-2 genes were constructed to infect B-lymphoblastoid cell lines from macaques. These cells were used as target cells for cytotoxicity assays with peripheral blood mononuclear cells from HIV-2BEN-infected cynomolgus macaques. To characterize the effector cells, CD8+ cells were separated with immunomagnetic beads. Major histocompatibility complex (MHC) restriction of the cytotoxic cells was determined by incubation with matched or mismatched target cells. HIV-2BEN-infected cynomolgus macaques raised CTL against proteins of the three major viral structural genes, gag, pol and env. The cytotoxic cells were CD8+ and their activity was MHC class I-restricted. In contrast to SIVmac-infected macaques, env-specific lysis was mediated exclusively by CD8+ cells. CTL from individual animals recognized different viral proteins and the recognition pattern varied over time. Like HIV-1 and SIVmac, HIV-2 induces virus-specific CTL. The variation of antigen recognition between individual animals and over time indicates that sequential experiments are necessary to determine the complete spectrum of the CTL response of infected animals. HIV-2-infected macaques represent a suitable model for investigations into the cellular immune response against HIV.


High-resolution structure of an HIV-1 quasispecies: identification of novel coding sequences. To characterize an HIV-1 quasispecies in vivo at high resolution (1%) in order to determine its genetic structure. The first coding exon of tat was amplified by polymerase chain reaction from uncultured peripheral blood mononuclear cells of an HIV-1-infected patient. The products were cloned into M13mp18 RF, and 106 clones were sequenced. Thirty-one different Tat protein variants were found. Amongst these, five major forms with frequencies of 44, 11, 8 and 5% were identified. All of the remaining 26 sequences were unique, 15 of which were defective. Within the variant spectrum a small number of genomes encoded novel open reading frames, for example, a tat-vpu fusion product. Some of the myriad proviruses present in an individual harbour novel coding sequences. While these are probably of little importance for AIDS pathogenesis they emphasize the ability of HIV to explore a huge range of genetic configurations.


Modulation of cell surface molecules during HIV-1 infection of H9 cells. An immunoelectron microscopic study. To study cell surface molecules and HIV-1 proteins on H9 cells 2 days after infection by immunogold electron microscopy, either in single or in double labelling using combinations of host cell-derived molecules and HIV-1 proteins. The presence of host cell antigens CD3, CD4 and human leukocyte antigen-DR (HLA-DR) and HIV-1 antigens gag p15, p17, p24 and env gp41 was evaluated using immunocytochemistry at the light microscopic level. H9 cells 2 days after infection were processed for conventional transmission electron microscopy and cryo-ultramicrotomy. Leukocyte antigens investigated were CD2, CD3, CD4 (two antibodies), CD5, CD8, CD25, CD30, CD63 antigens and HLA-DR; HIV-1-encoded antigens were gag p24, pol reverse transcriptase, and env gp41 and gp120. Double immunogold labelling was performed using reagents with different sized gold particles. For leukocyte markers, the labelling density of the cell membrane was assessed quantitatively on uninfected and infected H9 cells. Infected cells revealed the presence of gag p24, pol, and env gp41 and gp120 antigens on HIV-1 virions. Uninfected H9 cells showed a random distribution of cell surface molecules, including CD4 antigen, along the plasma membrane. The CD63 antigen, a lysosomal membrane glycoprotein, was located mainly in the cytoplasm of uninfected cells. Cells 2 days after infection showed CD4 labelling on sites where virions were budding from or attached to the cell surface and on free virions. Virions also showed labelling by CD3, CD5, CD25, CD30 and CD63 antibodies and anti-HLA-DR. Compared with uninfected cells, a significantly lower density was found on infected cells in labelling for CD4, CD5 and anti-HLA-DR. A significantly higher density on cells 2 days after infection was seen in CD63 labelling. During the first phase of infection host cell molecules concentrate on budding structures and newly generated HIV-1 virions. This phenomenon might contribute to the disappearance of these molecules (like the CD4 molecule) from the cell membrane after infection.


Vertical transmission of HIV-1: lack of detectable virus in peripheral blood cells of infected children at birth. To evaluate the time-course of HIV-1 detection in peripheral blood mononuclear cells (PBMC) from newborns at risk of vertically acquired infection. Forty-six infants born to HIV-1-infected mothers were enrolled at birth and examined virologically and clinically in the perinatal period and every 30 days for the first 3 months of life. Follow-up was conducted at intervals of 2-3 months. HIV-1 detection in PBMC was performed using virus culture and polymerase chain reaction (PCR) assay. Only one out of 24 newborns tested within 48 h of delivery and two out of 22 infants tested between 3 and 15 days of age were found to be HIV-1-positive by both PCR and virus culture. Further testing performed between 30 and 60 days of life identified an additional eight HIV-1-positive children. Subsequent viral, immunological and clinical follow-up confirmed PCR and virus culture results obtained in 30-60-day-old children. Infected infants had detectable levels of HIV-1 in their PBMC at 1 month of age. The negative PCR and virus culture findings in PBMC of newborns indicate strongly that HIV-1 cannot be diagnosed at birth in the majority of cases, and suggests that viral transmission could occur during late pregnancy and/or delivery.


Inhibition of HIV-1 productive infection in hepatoblastoma HepG2 cells by recombinant tumor necrosis factor-alpha. To evaluate the role of liver cells in and the effect of tumor necrosis factor-alpha (TNF-alpha) on HIV-1 replication. Human hepatoblastoma HepG2 cells were infected with various strains of HIV-1 and the effect of TNF-alpha treatment, either before or after infection, was monitored by p24 antigen assays. Northern blot analysis and gel retardation assays were performed to determine the expression of CD4 and HIV-1 trans-acting region (TAR)-binding proteins in these cells, respectively. HepG2 cells are CD4+ and support active HIV-1 replication, producing infectious virions, as measured by both p24 production and ability to infect T-cell lines with the virus produced by HepG2 cells. In contrast to the stimulatory effect of TNF-alpha on HIV-1 replication in T-cells and monocytes, up to 200 U/ml TNF-alpha treatment, at various times, either before or after HIV-1 infection, substantially inhibited p24 antigen production in HepG2 cells without causing any remarkable cytotoxicity. Gel-retardation assay revealed enhancement of a DNA-binding protein in TNF-alpha-treated HepG2 cells that binds to a specific sequence of the HIV-1 TAR, compared with the untreated control. These results indicate the importance of cellular factor(s) in HIV-1 infection and suggest that cytokines in different tissues can induce opposite effects. TAR-binding protein may act as an inhibitory factor for HIV-1 replication in the HepG2 cell line.


HIV-1 expression during early mammalian development. Our long-term objective is to determine the consequences of HIV-1 expression in the mammalian fetus using the mouse as a model system. This study describes HIV gene expression in micro-injected and electroporated embryos during the pre-implantation period. Procedures were adopted to create a non-infectious HIV system to assay HIV long terminal repeat (LTR) activation in a non-human mammal. Two constructs (RSV promoter-HIV tat gene; HIV LTR-lac Z gene) were co-micro-injected (10 micrograms/ml each) into pronuclei of fertilized eggs or one nucleus of the two-cell stage and expression assessed after 2-5 days. The techniques of electroporation and micro-injection were compared for their ability to deliver the constructs expressed subsequently. We found that HIV-1 expression, as monitored by beta-galactosidase production, can occur as early as the eight-cell to blastocyst stage. The intensity of HIV expression varied from high to low; the proportion of the embryo expressing HIV varied from half to only two cells. The material was too limited to allow a determination of integration. The expression rate of the HIV-LTR was low, averaging slightly over 1%. The data demonstrate that the HIV-LTR can be activated in early mammalian development, even before implantation. This information is valuable to those studying HIV-transgenic mice, to those interested in factors governing HIV expression, and to those concerned about pathologies accompanying developmental expression of HIV.


The absence of Tat sequences in tissues of HIV-negative patients with epidemic Kaposi's sarcoma. Tat, an essential regulatory protein of HIV, acts as a growth factor for Kaposi's sarcoma (KS)-derived cells in culture. We tested the hypothesis that HIV-negative epidemic KS patients who are also at high risk for HIV disease might have been infected with a defective HIV-1 virus that retained the ability to express Tat. We evaluated the presence of Tat sequences in KS tissue and peripheral blood mononuclear cells (PBMC) of HIV-1-negative individuals with epidemic KS who had risk factors for HIV infection by polymerase chain reaction using specific primers for the Tat region of HIV-1. No evidence for the presence of Tat-1 sequences or for Tat-expressing defective HIV-1 virus was found. These results suggest that HIV-1 Tat does not play a role in the initiation of KS in HIV-1-negative individuals. Tat might play an indirect role in epidemic KS in HIV-infected patients.


Systemic dissemination by a newly recognized intestinal microsporidia species in AIDS. Primarily to determine whether an intestinal microsporidian recently identified in AIDS patients disseminates from the bowel to infect other organs. Disseminated microsporidiosis has been reported in immunocompromised humans, but never due to Enterocytozoon bieneusi, the most common species in AIDS patients and one that evidently infects only enterocytes. In animals, dissemination follows ingestion of Encephalitozoon cuniculi spores, apparently via macrophages, and pathology occurs in, for example, kidneys and brain. A second, un-named Encephalitozoon-like intestinal microsporidia has been identified in five AIDS patients with chronic diarrhea; because it infects lamina propria macrophages, it was logical to investigate its dissemination. Light and transmission electron microscopy were used to study urine sediment from four out of five patients with biopsy-documented small intestinal infection due to the second intestinal microsporidian. The gall bladder from one patient and autopsy specimens from an E. bieneusi-infected patient were similarly studied. Systemic dissemination was documented by detecting abundant spores, both free and within renal tubular and transitional cells, in the urine of two patients. Many of the lamina propria macrophages in these two patients' intestinal biopsies contained microsporidia, while those of the two negative patients either contained only Mycobacterium avium complex or only occasional parasites. The gall bladder was co-infected with this microspordian and with cytomegalovirus. At autopsy, the patient with documented enteritis due to E. bieneusi 2 years before death had disseminated microsporidiosis, not of E. bieneusi, but apparently of the second intestinal species. The microsporidian had caused severe tubulointerstitial nephritis. Parasites were also observed in non-parenchymal cells of the liver and bronchial epithelium. A newly described Encephalitozoon-like intestinal microsporidian, which causes chronic diarrhea in AIDS patients, can disseminate and cause renal pathology.


Progressive spastic myelopathy in a patient co-infected with HIV-1 and HTLV-II: autoantibodies to the human homologue of rig in blood and cerebrospinal fluid. Human T-cell leukemia virus types I (HTLV-I) and II (HTLV-II) are closely related human retroviruses. HTLV-I has been implicated in a chronic progressive myelopathy, known as tropical spastic paraparesis (TSP) or HTLV-I-associated myelopathy (HAM). We sought to determine whether autoantibodies to brain antigens were present in the cerebrospinal fluid (CSF) of a patient with chronic progressive spastic myelopathy with evidence of both HIV-1 infection and HTLV-I/II seropositivity. A 54-year-old bisexual man with clinical features of HAM/TSP of over 20 years' duration was followed. We applied discriminatory DNA amplification (polymerase chain reaction) to distinguish HTLV-I from HTLV-II and to verify co-infection with HIV-1. The patient's CSF was used to screen a human brain cDNA expression library to identify antibodies directed against brain antigens. Autoreactive bacteriophage clones were isolated and sequenced. The patient was found to be co-infected with both HIV-1 and HTLV-II, but not with HTLV-I. HTLV-II proviral levels in the peripheral blood remained relatively constant, despite therapy with zidovudine. Prominent oligoclonal banding of immunoglobulins was present in the patient's CSF. A single repeatedly reactive cDNA clone was identified, by screening with CSF antibody, sequenced, and found to be the human homologue of the rat insulinoma gene, rig. HTLV-II infection may predispose to development of a HAM/TSP-like illness. Autoimmune mechanisms, such as autoantibody formation, may play a role in pathogenesis.


Tuberculous meningitis with acellular cerebrospinal fluid in AIDS patients. To describe the clinical manifestations of tuberculous meningitis in HIV-positive patients with acellular cerebrospinal fluid (CSF). Retrospective analysis of case reports. Four HIV-positive patients with acellular CSF and tuberculous meningitis are reported. Clinical presentation did not indicate meningeal infection in three of the four cases, and CSF tests were unusual in all cases. Two patients were diagnosed only after death. Acellular CSF may obstruct the diagnosis of tuberculous meningitis in AIDS patients.


Oral dapsone versus nebulized pentamidine for Pneumocystis carinii pneumonia prophylaxis: an open randomized prospective trial to assess efficacy and haematological toxicity. To compare the haematological toxicity and efficacy of oral dapsone and nebulized pentamidine as Pneumocystis carinii pneumonia (PCP) prophylaxis in HIV-infected patients receiving zidovudine. Randomized, prospective. Infectious diseases hospital with participants drawn from both inpatient and outpatient departments. Those eligible were starting treatment with zidovudine, needed PCP prophylaxis (CD4+ count < 200 x 10(6)/l or < 20% total lymphocyte count or previous episode of PCP), and had a normal glucose-6-phosphate dehydrogenase screen. Of the 98 patients enrolled, 96 returned for follow-up. Fifty patients received dapsone (100mg orally twice weekly) and 46 pentamidine (400 mg nebulized monthly). Follow-up was for a median of 18 months. The development of PCP, transfusion requirements, monthly complete blood cell counts, serious adverse reactions and death were recorded. Nine (18%) dapsone and eight (17%) pentamidine recipients developed PCP. There was no significant difference in number of patients transfused (12 dapsone and nine pentamidine recipients) or transfusion-free survival. At exit from the study, mean haemoglobin (11.7 versus 12.4 g/dl), white blood cell (3.9 versus 3.7 x 10(9)/l) and platelet (195 versus 184 x 10(9)/l) counts did not differ for the dapsone and pentamidine arms, respectively. There was no significant difference in the occurrence of serious adverse reactions (six in the dapsone and eight in the pentamidine arm). Dapsone can be recommended in preference to pentamidine as PCP prophylaxis on the basis of equivalent efficacy, absence of excessive haematological toxicity, low cost and ease of administration.


Rapid increase of both HIV-1 infection and syphilis among pregnant women in Nairobi, Kenya. To determine the prevalence of HIV-1 and syphilis antibodies in a population of pregnant women in Nairobi, Kenya, between 1989 and 1991. As part of an ongoing prospective study on the effect of HIV-1 infection and sexually transmitted diseases, 4883 pregnant women were screened for HIV-1 and syphilis antibodies in one health-centre in Nairobi. HIV-1 seroprevalence increased from 6.5 to 13.0% (P < 0.001) and syphilis seroreactivity from 2.9 to 5.3% (P = 0.002), while there was no change in gonococcal infection rates. The most rapid increase in HIV-1 prevalence was observed in women aged less than 25 years. There was no evidence of demographic fluctuations in the population during this time, or of changes in sexual behaviour, except that fewer women enrolled in 1991 reported having more than one sex partner, compared with women enrolled in 1989 (39.1 versus 20.0%; P = 0.0001). HIV-1-seropositive women were more likely to be seroreactive for syphilis than HIV-1-seronegative mothers (7.7 versus 3.2%; odds ratio = 2.5; 95% confidence interval, 1.7-3.8; P < 0.001), but there was no difference between the two groups in terms of gonorrhoea prevalence. These data confirm an association between HIV-1 and syphilis infection, and indicate that both are spreading rapidly among women in Nairobi outside high-risk groups. Increased efforts to control both infections are urgently required.


Women and HIV infection: a cohort study of 483 HIV-infected women in Bordeaux, France, 1985-1991. The Groupe d'Epidémiologie Clinique du SIDA en Aquitaine. To study the epidemiological trends, clinical patterns, evolution and prognosis of HIV infection in women. Cohort study of 1816 HIV-infected patients. Up to 1 January 1991, 483 (26.6%) of the patients reported to the Groupe d'Epidemiologie Clinique du SIDA en Aquitaine surveillance system were women. The male-to-female ratio has decreased progressively (3.4:1 in 1985; 2.7:1 in 1990) over time. Fifty per cent of HIV-infected women are or have been intravenous drug users (IVDU). The proportion of heterosexually acquired HIV infection increased from 11.6 to 34.6% over the last 5 years; 46.9% of the women infected through heterosexual intercourse reported sexual contacts with male IVDU. Excluding Kaposi's sarcoma, no significant difference was observed between men and women in the overall distribution of AIDS-defining events. The observed trend of a slower progression to AIDS in women, compared with men, disappeared when controlling for prognostic variables. However, female sex significantly enhanced survival after AIDS diagnosis in multivariate analysis (relative risk, 2.7; 95% confidence interval, 1.1-6.2). Early diagnosis of HIV infection in female patients and prevention of HIV infection among women is now a priority for public health interventions, both in industrialized and in developing countries.


Abortions and HIV-1 infection in New York City, 1987-1989. This serologic survey was performed to determine rates of HIV-1 infection among New York City (NYC) women seeking abortions. Anonymous unlinked blood samples were collected and analyzed for the presence of HIV-1 antibodies. Abortion clinics were chosen for the representativeness of their patient population to all women obtaining abortions in NYC. Blood samples and demographic information, including age group, race/ethnicity, borough of residence and type of payment were obtained from 15 abortion sites (11 clinics, four hospitals) in NYC between 1987 and 1989. A total of 5889 blood samples were collected from women seeking abortions. Twelve of the 15 facilities were sampled in all 3 years. We determined HIV infection rates in the overall sample and in selected subpopulations, and assessed temporal trends. Stepwise logistic regression was applied to identify factors independently associated with HIV-1 infection. The rate of HIV-1 infection in the overall sample was 1.19% (70 out of 5889) and remained stable in the 12 facilities sampled during all 3 years: 1987 (1.42%, 17 out of 1200); 1988 (1.67%, 20 out of 1200); and 1989 (0.90%, 27 out of 2989) (P = 0.09). Logistic regression identified receiving Medicaid and being aged between 25 and 35 years to be independently associated with HIV-1 infection. Approximately 1200 women seeking abortions annually in NYC are infected with HIV-1. If accessibility to elective abortion is curtailed, the number of children born to HIV-1 infected mothers will increase.


Tuberculosis incidence in developing countries with high prevalence of HIV infection. To study the impact of the HIV epidemic on tuberculosis (TB) incidence in developing countries. A simple mathematical model is constructed using figures from published reports to estimate the rise of TB incidence as the HIV epidemic expands. Two groups with different risk of developing TB are identified: individuals with dual infection of HIV and Mycobacterium tuberculosis and the rest of the population. The model is based on a combination of the incidence and the percentage of TB in these two groups. The expected rise in TB incidence and the percentage of TB cases that will be HIV-positive are plotted against the prevalence of HIV. Unless appropriate action is taken, TB incidence in developing countries will double as the prevalence of HIV infection reaches 13 per hundred adults.


Longitudinal sexual behavior changes in injecting drug users. To determine whether injection drug users (IDU) maintained sexual behavior risk reduction over an 18-month period that had been noted previously over a 4-month period. A repeated measures design was utilized with IDU assessed initially at study enrollment and again 18 months later. Sexual behaviors of a group of 220 IDU (148 men and 72 women) were assessed by a structured interview at the start of an AIDS prevention project and again 18 months later. Having multiple sex partners during the 12 months before initial assessment was reported by 42.6% of the men and 35.7% of the women. Significantly fewer had multiple sex partners during the 10 months before follow-up assessment (men, 20.9%; women, 14.3%). Condom use for vaginal intercourse increased from a mean of 11.9% initially to 27.8% at follow-up for men. The increase in condom use was greater for those with multiple sex partners. Women did not report significant increases in condom use. Continued involvement in unsafe sexual behaviors was associated with exchanging sex for money or drugs, using drugs to help meet sexual needs, alcohol use and drug use. Risk reductions noted previously were maintained over 18 months for the majority of the sample. Drug-use treatment and interventions that closely examine the interplay between drug use and sexuality for individual IDU are recommended as strategies to further reduce the sexual risk of HIV transmission among IDU.


Nursing in Latvia from the perspective of Oppressed Theory. Few nurses have the opportunity to witness the rebirth of a democratic state. The author, an American nurse of Latvian birth, served as a visiting professor at the Latvian Medical Academy, Department of Nursing, three weeks after Latvia had declared independence in August, 1991 during the coup d'etat of the Union of the Soviet Republics (USSR). In this article, the author shares and discusses her cultural experiences and reflections of Latvia from oppressed group theory perspectives. In an ever increasing pluralistic society, the author believes that nurses need the widening perspective of transcultural nursing to understand populations and changes in Eastern Europe. She further contends that nurses need a full understanding of what developed with the Latvians and what they have experienced during the last fifty years under communism.


Transcultural nursing care values, beliefs, and practices of American (USA) Gypsies. This ethnonursing qualitative investigation was focused on the domain of culture care values, expression and meanings of selected American Gypsies. The purpose of the study was to explicate culture care American Gypsy lifeways in order to help nurses understand this largely unknown culture, and to offer guidelines for providing culturally congruent nursing care. Leininger's theory of Culture Care Diversity and Universality was the appropriate theory to use for this study, along with the ethnonursing research method to generate emic and etic grounded data. Findings substantiated that the world view, ethnohistory, religion (moral code), kinship and cultural values, and generic folk practices were powerful influences of Gypsy lifeways and supported culture congruent nursing care. Ethnohistorical facts strongly buttressed the cultural values, norms, and moral codes for culture specific care practices. Several Gypsy culture specific and dominant care meanings, expressions, and actions were confirmed and made credible from raw data and thematic analysis. They were: 1) protective in-group caring; 2) watching over and guarding against Gadje; 3) facilitating care rituals; 4) respecting Gypsy values; 5) alleviating Gadje harassment; 6) remaining suspicious of outsiders; and 7) dealing with purity and impurity moral codes and rules. Culture specific and congruent care generated from Leininger's theory with the three predicted modes were identified to guide nursing decisions and actions.


Pregnancy and childbirth beliefs and practices of American Hare Krishna devotees within transcultural nursing. The followers of Krishna Consciousness are primarily young men and women of child-bearing age who desire healthy pregnancies within the beliefs and practices of their particular culture. The researcher spent a year and a half with American Hare Krishna devotees in a large Southeastern city and on a farm in a neighboring state. The researcher used Leininger's Cultural Care Theory and the ethnographic qualitative research method to focus on the ethnohistory, social structures, and care and caring beliefs and practices of the group related to pregnancy and childbirth. Transcultural nursing implications were derived from the study. While the research was done in 1981 and 1982, the researcher has been back to visit the Krishna devotees several times. Contact with other Krishna followers in different places has also been accomplished since the study. The researcher has found that the same cultural beliefs, practices, and values have prevailed within the group over the years.


Lateral dorsal cutaneous branch of the sural nerve. Standardization in nerve conduction study. Lateral ankle or foot pain may have various etiologies including entrapment of or injury to the distal sural nerve or early peripheral neuropathy. Antidromic distal sural conduction studies have not been used in clinical neurophysiologic evaluation, however, for technical reasons. The purpose of this study was to determine if by modifying recording parameters and using electronic averaging adequate responses could be obtained to permit standardization of distal sural conduction. Standard surface recording electrodes with an inter-electrode separation of 37 mm were used. The distal sural nerve conduction of 40 healthy adult subjects (mean age = 33 +/- 9 yr, range = 23 to 52) was measured. The latency to the onset was 3.2 +/- 0.4 ms (range = 2.5 to 4.0 ms) and to the negative peak was 3.9 +/- 0.5 ms (range = 3.0 to 4.9 ms). The conduction velocity was 38 +/- 5 m/s (range = 30 to 48 m/s). The amplitude measured from baseline to negative peak was 5.8 +/- 2.1 microV (range = 3.0 to 11.0 microV). The results indicated that electrodiagnostic evaluation of the distal sural nerve could be readily achieved and that this might be useful in differential diagnosis.


Continuous intrathecal baclofen in spinal cord spasticity. A prospective study. Continuous intrathecal infusion of the well known antispastic medication baclofen was evaluated in ten consecutive patients. One year after pump implantation the average Ashworth scale for muscle tone decreased, compared with before treatment, 2.32 points (P < 0.0001), reflexes decreased 2.22 points (P < 0.0001) and the spasm score decreased 1.65 points (P < 0.0001). The average dose increased from 92.22 to 290.95 micrograms (P < 0.0001) between the 1st month of treatment and 1 yr of treatment. The dosage for all patients more than doubled (P < 0.0022) between 3 months and 1 yr postimplantation. There was no significant difference for muscle tone, reflexes or spasms at 3 months v 1 yr. Complications were not unusual and included temporary atelectasis, orthostatic hypotension with escalation of baclofen dose, loss of penile erections, postsurgical pseudo-meningoceles, catheter disruptions and exhausted pump reservoirs. One patient suffered a seizure apparently related to a rapid withdrawal from intrathecal baclofen as a result of catheter sequestration. All patients required a period of intensive inpatient rehabilitation to benefit functionally from the decreased motor tone and/or increased voluntary motor control. The procedure is expensive and close follow-up is necessary for assessing efficacy and refilling the pump. Intrathecal baclofen infusion by subcutaneous pump is useful in treating the effects of spinal spasticity resistant to oral medications. However, there appears to be accommodation to intrathecal baclofen necessitating escalating doses to maintain clinical effects.


Hormone changes in men with spinal cord injuries. The steady state profiles of 63 men with traumatic spinal cord injuries (24 quadriplegics and 39 paraplegics; average age of 31.2 +/- 6.8 yr; 18-44 yr) were studied. The average length of post-traumatic period was 6.2 +/- 5.0 yr, ranging from 8 months to 20 yr. It was found that all the subjects had normal serum thyroxine, thyrotropin, cortisol, growth hormone and plasma adrenocorticotropic hormone. Seven cases (11.1%) had low serum triiodothyronine and eight cases (12.7%) had low serum testosterone. On the other hand, 17 cases (27.0%) had hyperprolactinemia; 9 cases (14.3%) had elevated serum testosterone level; 6 cases (9.5%) had elevated serum follicle-stimulating hormone; and 4 cases (6.3%) had elevated serum luteinizing hormone. The level of spinal cord injury, injury period and patient age had no correlation with other serum hormone changes except that quadriplegic subjects had lower serum triiodothyronine than the paraplegic, with a mean of 1.42 +/- 0.30 v 1.70 +/- 0.36 nmol/liter (P < 0.005). Of the eight subjects who had low serum testosterone, none had elevated gonadotropin. There were also eight subjects with elevated follicle-stimulating hormone and/or luteinizing hormone, six of them had normal serum testosterone and two had elevated serum testosterone. This suggested their hypogonadism did not result primarily from classic primary gonadal failure. It could be speculated that other testicular paracrine factors and/or alteration of hypothalamus-pituitary-testicular axis are involved in the pathogenesis of hypogonadism. Further studies in this field will provide information regarding male reproductive physiology and may have impact on fertility enhancement options for men with spinal cord injuries.


A clinical trial of strengthening and aerobic exercise to improve gait and balance in elderly male nursing home residents. The purpose of this study was to determine whether a moderate to high intensity strengthening and aerobic exercise program can improve the strength, exercise capacity, gait and balance of deconditioned male nursing home residents. Ambulatory subjects who scored 30 or less on the modified Tinetti gait and balance assessment scale, who demonstrated less than 80% of age-matched lower extremity strength on isokinetic muscle testing and who gave informed consent were enrolled. Subjects were randomized to either an exercise (n = 8) or a control (n = 6) group. All participants underwent an exercise test to determine maximal oxygen uptake (VO2max) and received quantitative gait and balance measurements. The subjects assigned to the exercise group than completed a 12-wk program of weight training for the lower extremities and stationary cycling. Both the exercise and control groups were then retested. Ten outcome variables were assessed: Tinetti mobility scores, VO2max, isokinetic-tested lower extremity strength and endurance, stride length, gait velocity, stance time, gait duration, cadence and balance. The exercise group, after completion of the program, demonstrated significant improvements in Tinetti mobility scores (P < 0.05), combined right and left quadricep muscle strength (P < 0.01), right and left lower extremity muscular endurance (P < 0.01), left stride length and gait velocity (P < 0.05), although other outcome variables changed insignificantly. The control group revealed no changes of significance with the exception of improvement of the combined right and left hamstring muscle strength (P < 0.05). Nevertheless, for those outcome variables that had improved significantly in the exercise group, the changes amounted to only a 5 to 10% increase over the baseline measurements. These findings showed that an appropriately designed high intensity exercise program can result in significant although limited improvements for clinical mobility scores, strength, muscular endurance and certain gait parameters.


Fibromyalgia syndrome. New associations. Previous research has demonstrated a number of conditions, such as sleep disturbance, fatigue, depression, spastic colon and mitral valve prolapse, associated with fibromyalgia. The present report describes additional symptoms and medical conditions that appear to be associated with the syndrome based on a survey of 554 individuals with fibromyalgia compared with a group of 169 controls. Individuals with fibromyalgia self report a greater incidence of bursitis, chondromalacia, constipation, diarrhea, temporomandibular joint dysfunction, vertigo, sinus and thyroid problems. Symptomatic complaints found statistically more prevalent in fibromyalgia patients included concentration problems, sensory symptoms, swollen glands and tinnitus. Other associations occurring with significant increased frequency were chronic cough, coccygeal and pelvic pain, tachycardia and weakness. Our previous report on inheritance patterns in fibromyalgia was reaffirmed with 12% reporting symptomatic children and 25% reporting symptomatic parents. Of the respondents, 70% noted that their symptoms were aggravated by noise, lights, stress, posture and weather.


Spinal cord arteriovenous malformation in a person with congenital lymphatic abnormalities. Spinal cord arteriovenous malformations have been described in association with a variety of congenital diseases affecting the vasculature, including Klippel-Trenaunay-Weber syndrome, Rendu-Osler-Weber syndrome and others, but rarely in association with lymphatic abnormalities. We report the case of a young man with congenital lymphedema and arteriovenous malformations of one lower extremity and a spinal cord arteriovenous malformation. Awareness of the possible presence of a central nervous system arteriovenous malformation in individuals with pre-existing arteriovenous and lymphatic abnormalities may be helpful in their diagnosis and management.


Dural tear following traumatic spinal cord injury. A delayed complication. Dural tears with leakage of cerebral spinal fluid into surrounding soft tissues can occur after traumatic spinal cord injury. An unusual case presented in a patient with traumatic paraplegia where the onset was delayed and clinical features were suggestive of autonomic dysfunction. The clinical features, pathophysiology and treatment of this interesting complication following traumatic spinal cord injury are discussed.


Pergolide can induce soluble superoxide dismutase in rat striata. Pergolide, a dopamine receptor agonist, given daily i.p. for three weeks at 0.04 mg/kg and 0.4 mg/kg, significantly induced soluble (Cu-Zn) superoxide dismutase in the rat striatum, while having no effect on the mitochondrial (Mn) form of the enzyme. Such induction, which can also be effected by (-)-deprenyl, may help to protect against nigrostriatal degeneration.


Photoperiodic response of pineal-thyroid axis of the female Indian palm squirrel, Funambulus pennanti. Effect of short (SP: 10 L: 14 D: Light: Dark) and long (LP: 14 L: 10 D) photoperiod was tested on pineal-thyroid axis in a tropical seasonally breeding rodent F. pennanti during sexually regressive phase of reproduction. SP reduced thyroid weight and plasma thyroxine (T4) as well as increased melatonin (aMT) while pinealectomy (Px) prevented such an effect of SP. LP and Px plus LP had no significant effect on thyroid activity when compared with their respective controls. These results suggest that SP stimulated pineal activity which increased the concentration of aMT, hence inhibited thyroid gland activity. However, the plasma aMT concentration under LP regime had no significant difference from controls, as the ambient photoperiodic length (13.6 hr) was almost similar to the experimental one (14.0 hr). It is suggested that being innervated from the same ganglion (SCG) which conveys photic stimuli to the pineal gland, the thyroid gland like the pineal is also under the influence of photoperiodic responses. Further pineal/melatonin also influences thyroid function indirectly.


Changes in the amount and distribution of neuronal alkaline and acid phosphatase after chronic exposure of cultures of cingulate cortex to antidepressant drugs. Enzyme histochemistry was used to examine alkaline and acid phosphatases in cultures of embryonic rat cingulate cortex after 14 days exposure in vitro to two tricyclic antidepressants (amitriptyline and desipramine) and two non-tricyclic antidepressants (mianserin and citalopram). An increased amount of acid phosphatase reaction product was observed in lysosomes of neurons in cultures treated chronically with the non-tricyclic antidepressants, mianserin or citalopram. More strikingly, reaction product was also present in the inner lamellae of the Golgi apparatus after this treatment, but never in controls. These observations suggest that non-tricyclic antidepressants significantly increase the rate of degradative processes in cingulate neurons. In cultures, treated chronically with desipramine or amitriptyline, pre- and postsynaptic membranes contained heavy deposits of alkaline phosphatase reaction product, whereas in control cultures not exposed to these drugs the corresponding membranes were entirely devoid of reaction product. An increase in the amount of alkaline phosphatase reaction product was also observed on the plasma membranes of neuronal cell bodies. These observations suggest that chronic exposure to antidepressants may influence transmembrane transport in cingulate neurons.


Effects of fenfluramine on plasma homovanillic acid in healthy subjects. The specificity of fenfluramine as a pharmacological probe of the serotonin system has been questioned, since animal studies with high dose l-fenfluramine show increases in striatal levels of the dopamine metabolite homovanillic acid. To test the specificity of fenfluramine in humans with clinical doses, we compared plasma homovanillic acid (pHVA) concentration in healthy volunteers after administration of fenfluramine (60 mg) and placebo. There were no significant effects on pHVA, which supports previous findings that at doses used in pharmacological challenge paradigms, the effect of fenfluramine on the dopamine system is insufficient to alter measures of its change.


Vehicle occupant exposure to carbon monoxide. This paper focuses on the auto commuting micro-environment and presents typical carbon monoxide (CO) concentrations to which auto commuters in central Riyadh, Saudi Arabia were exposed. Two test vehicles traveling over four main arterial roadways were monitored for inside and outside CO levels during eighty peak and off-peak hours extending over an eight-month period. The relative importance of several variables which explained the variability in CO concentrations inside autos was also assessed. It was found that during peak hours auto commuters were exposed to mean CO levels that ranged from 30 to 40 ppm over trips that typically took between 25 to 40 minutes. The mean ratio of inside to outside CO levels was 0.84. Results of variance component analyses indicated that the most important variables affecting CO concentrations inside autos were, in addition to the smoking of vehicle occupants, traffic volume, vehicle speed, period of day and wind velocity. An increase in traffic volume from 1,000 to 5,000 vehicles per hour (vph) increased mean CO level exposure by 71 percent. An increase in vehicle speed from 14 to 55 km/h reduced mean CO exposure by 36 percent. The number of traffic interruptions had a moderate effect on mean concentrations of CO inside vehicles.


Ultrasound beam orientation during standard two-dimensional imaging: assessment by three-dimensional echocardiography. Standard two-dimensional echocardiographic image planes are defined by anatomic landmarks and assumptions regarding their orientation when these landmarks are visualized. However, variations of anatomy and technique may invalidate these assumptions and thus limit reproducibility and accuracy of cardiac dimensions recorded from these views. To overcome this problem, we have developed a three-dimensional echocardiograph consisting of a real-time scanner, three-dimensional spatial locater, and personal computer. This system displays the line of intersection of a real-time image and an orthogonal reference image and may be used to assess actual image orientation during standardized two-dimensional imaging when the line-of-intersection display is not observed by the operator. Three hundred forty standard images were assessed from 85 examinations by 11 echocardiographers. Twenty-four percent of the unguided standard images were optimally positioned within +/- 5 mm and +/- 15 degrees of the standard. Of the optimal images, two thirds were parasternal long-axis views. A subsequent study with three-dimensional echocardiography and line-of-intersection guidance of image positioning showed 80% of the guided images to be optimally positioned, a threefold improvement (p < 0.001). Two-dimensional echocardiography does not achieve reasonably consistent optimal positioning of standard imaging views, suggesting that measurements taken from these views are likely to be suboptimal. Three-dimensional echocardiography that uses line-of-intersection guidance improves image positioning threefold and should therefore improve the accuracy and reproducibility of quantitative echocardiographic measurements derived from these images.