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Biomedical subjects

A Song

Publications and source records attributed to A Song.

At least 19 recordsLinked to original sources

Steroid-induced ptosis: case studies and histopathologic analysis.

PURPOSE: The purpose of this study was to review patients who developed ptosis after subtenon's steroid injection and to study the mechanism of steroid-induced ptosis in an animal model. METHODS: Part 1. Twenty-two patients with uveitis who had received posterior subtenon's triamcinolone acetonide injections were retrospectively reviewed. Demographics, type of uveitis, type and number of surgeries, pre and postoperative marginal reflex distance (MRD1), and clinical outcomes were evaluated. Part 2. Study of rabbit levator muscle and aponeurosis histopathology after subtenon's triamcinolone injection was performed. RESULTS: Part 1. The average age was 44.6 years (range: 14-85 years) with a mean follow-up of 14 months. The most common causes of uveitis included uveitis after cataract extraction (five), pars planitis (three), multifocal choroiditis (three), and juvenile rheumatoid arthritis (three). The average time to documented onset of ptosis was 13.9 months (range: 0-49 months). In patients who received only one steroid injection, the average time to ptosis recorded was 2.7 months (range: 0-6 months). Seventeen patients underwent ptosis repair. Part 2. No ptosis was noted in the experimental and control groups. Histopathologic analysis of levator tissues revealed no significant difference in atrophy or degree of inflammation between experimental and control groups. CONCLUSIONS: Ptosis following subtenon's steroid injection ranged from mild to moderate and occurred a few months after steroid injection. Prior studies of muscles and periocular tissues exposed to corticosteroids demonstrated degenerative muscle changes; our studies revealed no histopathologic changes in the levator muscle or aponeurosis.

Adolescent↗

Trends and predictors of HIV-positive community attachment among PLWHA.

Communities most affected by HIV/AIDS have been instrumental in shaping Australia's responses to the threat of the epidemic. There are recent signs that levels of engagement in communities based around HIV-positivity have changed: a diminished sense of an AIDS crisis, the relative success of highly active antiretroviral therapy (HAART), and an increasing individualization of the HIV experience may be contributing to changes in the way HIV-community is experienced. In this paper, we explore levels of engagement in HIV-positive community among a cohort of people living with HIV/AIDS (PLWHA) and seek to explain why some PLWHA engage in an HIV-positive community while others do not. Using multivariate logistic regression, we found that three factors were independently related to feeling part of an HIV-positive community: having been diagnosed with HIV prior to the advent of HAART; having more recently taken Bactrim or Septrin for PCP; and finding it easier to take 'pills' on time. Taken together, these results suggest that both historical effects, such as the introduction of HAART, and effects related to living with HIV, such as the experience of an AIDS-related illness, help explain HIV-positive community engagement among PLWHA.

Acculturation↗

Pseudomonas aeruginosa in vitro corneal isolate sensitivity to ofloxacin, ciprofloxacin, and trovafloxacin: a comparative study.

PURPOSE: To compare sensitivity of Pseudomonas aeruginosa corneal isolates to ofloxacin, ciprofloxacin, and trovafloxacin. METHODS: Sensitivities of P. aeruginosa corneal isolates to each antibiotic from the periods 1985 to 1987 (n = 32) and 1995 to 1999 (n = 85) were evaluated in vitro with E tests (AB Biodisk; Remel, Lenexa, Kansas). RESULTS: Overall, the percent of P. aeruginosa corneal isolates sensitive in vitro to ofloxacin (106/117, 90.6%) was significantly less than to ciprofloxacin (113/117, 96.6%, P =.016) and trovafloxacin (113/117, 96.6%, P =.016). We observed trends of decreasing sensitivity to ciprofloxacin and trovafloxacin, which were not statistically significant. Sensitivity to ofloxacin remained unchanged; however, sensitivity to ofloxacin was always less than sensitivity to ciprofloxacin and trovafloxacin. CONCLUSION: Although in vitro susceptibilities may not correlate with in vivo efficacy, our data suggest that ciprofloxacin and trovafloxacin are superior to ofloxacin in the treatment of P. aeruginosa keratitis.

Anti-Infective Agents↗

Functional activation of the extensor carpi radialis muscles in humans.

OBJECTIVES: To assess activity of radial wrist extensors caused by isometric radial deviation and extension by using magnetic resonance imaging (MRI) and to assess measures that might be used to normalize T2-weighted data. DESIGN: Two-way analysis of variance (ANOVA) design. SETTING: Laboratory and children's hospital. PARTICIPANTS: Three healthy volunteers. INTERVENTIONS: Ten repetitions of 10-second randomly ordered 30% or 60% of maximum voluntary isometric contractions toward wrist extension or radial deviation. MAIN OUTCOME MEASURES: Average T2 values from T2-weighted MR images of the extensor carpi radialis brevis (ECRB) and the extensor carpi radialis longus (ECRL), flexor digitorum profundus (FDP), and radius marrow were determined across 7 sections and 4 exercise bouts and a preexercise condition. RESULTS: Significant differences across task and across sections were determined. Post hoc analysis revealed differences in activity between proximal and distal ECRB and ECRL during an exercise and differential activation of the same muscle across the 2 exercise tasks. Bone marrow and FDP did not show task-related changes. The range of average T2 values of bone marrow across sections was greater than a muscle (FDP) that was not the target of the exercise protocol. However, FDP did show small but significant differences across sections. CONCLUSIONS: T2-weighted MR images can be used to study muscle activation at 30% and 60% of maximum voluntary contractions. The use of inactive muscle and bone marrow for normalizing data requires further investigation.

Adult↗

Serine protease inhibitor causes F-actin redistribution and inhibition of calcium-mediated secretion in pancreatic acini.

BACKGROUND & AIMS: The present study was undertaken to evaluate the role of serine proteases in regulating digestive enzyme secretion in pancreatic acinar cells. METHODS: Isolated acini were stimulated by various secretagogues in the presence or absence of cell-permeant serine protease inhibitors 4-(2-aminoethyl)-benzenesulfonyl fluoride and N(alpha)-p-tosyl-L-phenylalanine chloromethyl ketone. F-actin distribution was studied after staining with rhodamine phalloidin. RESULTS: Both cell-permeant serine protease inhibitors blocked amylase secretion in response to secretagogues that use calcium as a second messenger (e.g., cerulein, carbamylcholine, and bombesin) but not to those that use adenosine 3',5'-cyclic monophosphate (cAMP) as a second messenger (e.g., secretin and vasoactive intestinal polypeptide). Incubation of the acini with these inhibitors also resulted in a dramatic redistribution of the F-actin cytoskeleton. This redistribution was energy dependent. Similar redistribution of F-actin from the apical to the basolateral region was also observed when acini were incubated with a supramaximally stimulating concentration of cerulein, which is known to inhibit secretion. CONCLUSIONS: These results suggest that a serine protease activity is essential for maintaining the normal apical F-actin distribution; its inhibition redistributes F-actin from the apical to the basolateral region and blocks secretion induced by secretagogues that act via calcium. cAMP reverses the F-actin redistribution and hence cAMP-mediated secretion is not affected.

Actins↗

Organization of regions with amphiphilic alpha-helical potential within the three-dimensional structure of beta-sheet proteins.

The observation that strong amphiphilic alpha-helical potential exists in all proteins, including beta-sheet proteins, has given rise to the idea that alpha-helical intermediates may be critical to the folding paths of all proteins. Here we report that regions with amphiphilic alpha-helical potential in beta-sheet proteins are regularly spaced within the native structure of the proteins at an average interval of about 13 A. This regular spacing did not occur when the location of amphiphilic regions was randomly assigned (p = 0.0056), suggesting some degree of organization with respect to the native fold. However, in the native structure of various non-homologous proteins that contain the same fold, the location of the regions with amphiphilic alpha-helical potential was not conserved. Further, there was no apparent association of amphiphilic alpha-helical potential with any particular type of secondary structure, confirming that this potential is not involved in maintenance of native structure and suggesting that it may be associated with a highly adaptable process.

Models, Molecular↗

The LN54 radiation hybrid map of zebrafish expressed sequences.

To increase the density of a gene map of the zebrafish, Danio rerio, we have placed 3119 expressed sequence tags (ESTs) and cDNA sequences on the LN54 radiation hybrid (RH) panel. The ESTs and genes mapped here join 748 SSLp markers and 459 previously mapped genes and ESTs, bringing the total number of markers on the LN54 RH panel to 4226. Addition of these new markers brings the total LN54 map size to 14,372 cR, with 118 kb/cR. The distribution of ESTs according to linkage groups shows relatively little variation (minimum, 73; maximum, 201). This observation, combined with a relatively uniform size for zebrafish chromosomes, as previously indicated by karyotyping, indicates that there are no especially gene-rich or gene-poor chromosomes in this species. We developed an algorithm to provide a semiautomatic method for the selection of additional framework markers for the LN54 map. This algorithm increased the total number of framework markers to 1150 and permitted the mapping of a high percentage of sequences that could not be placed on a previous version of the LN54 map. The increased concentration of expressed sequences on the LN54 map of the zebrafish genome will facilitate the molecular characterization of mutations in this species.

Animals↗

Mutual information analysis as a tool to assess the role of aneuploidy in the generation of cancer-associated differential gene expression patterns.

Most human tumors are characterized by: (1) an aberrant set of chromosomes, a state termed aneuploidy; (2) an aberrant gene expression pattern; and (3) an aberrant phenotype of uncontrolled growth. One of the goals of cancer research is to establish causative relationships between these three important characteristics. In this paper we were searching for evidence that aneuploidy is a major cause of differential gene expression. We describe how mutual information analysis of cancer-associated gene expression patterns could be exploited to answer this question. In addition to providing general guidelines, we have applied the proposed analysis to a recently published breast cancer-associated gene expression matrix. The results derived from this particular data set provided preliminary evidence that mutual information analysis may become a useful tool to investigate the link between differential gene expression and aneuploidy.

Aneuploidy↗

Reduced inflammatory response to plasmid DNA vectors by elimination and inhibition of immunostimulatory CpG motifs.

An inflammatory response is invariably associated with administration of gene transfer complexes composed of cationic lipids and plasmid DNA (pDNA). In the lung, an influx of neutrophils and elevated levels of several proinflammatory cytokines such as TNF-alpha, IFN-gamma, IL-6, and IL-12 characterize this dose-dependent response. The induction of these cytokines was shown previously to be due in part to the presence of unmethylated CpG dinucleotides in the bacterially derived pDNA. We have eliminated 270 of 526 CpG dinucleotides in a reporter plasmid (pCFA-CAT) and tested the inflammatory response to cationic lipid:pDNA complexes containing the modified vector (pGZA-CAT) after intravenous (i.v.) or intranasal (i.n.) delivery into BALB/c mice. Compared to the unmodified vector, the CpG-reduced pGZA-CAT was found to be significantly less immunostimulatory, as the levels of IL-12, IFN-gamma, and IL-6 in the serum 24 h after i.v. delivery were reduced by 40 to 75%. Similar reductions in cytokine levels were also observed in the bronchoalveolar lavage fluids (BALF) after i.n. administration, while the levels of reporter gene expression were not affected by the modifications. We have also investigated known inhibitors of the CpG signaling pathways in order to decrease the inflammatory response. Two such inhibitors, chloroquine and quinacrine, greatly reduced the induction of IL-12 from mouse spleen cells in vitro and inhibited cytokine production in the lung by approximately 50% without affecting gene expression. These results illustrate that use of a less immunostimulatory pDNA vector or inhibitors of CpG immunostimulation can reduce significantly the toxicity associated with cationic lipid:pDNA complexes thereby increasing the therapeutic index of this synthetic gene transfer vector.

Administration, Intranasal↗

MR imaging of pentalogy of Cantrell variant with an intact diaphragm and pericardium.

We present a case of a neonate with the stigmata for pentalogy of Cantrell with the exception of diaphragmatic and pericardial defects. Diagnosing most of the anomalies in this rare syndrome can be accomplished using conventional modalities in radiology, but difficulties may arise determining diaphragmatic continuity. Accurate, early diagnosis of components of this syndrome is vital for surgical planning and assessing prognostic factors.

Abnormalities, Multiple↗

Development of the rat phrenic nucleus and its connections with brainstem respiratory nuclei.

The development of phrenic motoneurons and descending bulbospinal projections to the cervical spinal cord have been examined in prenatal and early postnatal rats with the aid of the carbocyanine dyes DiI and DiA. Phrenic motoneurons could be identified by retrograde labelling as early as E13, while aggregation of phrenic motoneurons into a column and the formation of dendritic bundles became apparent from E16. The initial phrenic motoneuron dendritic bundles were oriented in the dorsolateral and ventromedial directions, while ventrolaterally directed bundles entering the marginal zone appeared by E16, and rostrocaudal bundles were clearly visible by E21. The column of phrenic motoneurons extended rostrocaudally from C2 to C6 at E13 and E14, but this became confined to the C3-5 segments by E21. Two-way tracing of connections between putative brainstem respiratory centres and cervical spinal cord with the carbocyanine dyes, DiI and DiA, indicated that brainstem bulbospinal neurons in the position of the adult ventral respiratory group (VRG) and medial parabrachial (MPB) nuclei appeared to project to the cervical cord white matter as early as E15 and may contribute axons to the grey matter of the cervical cord as early as E17 These findings are consistent with electrophysiological studies of respiratory function development in the fetal rat, which found relatively regular rhythmic phrenic discharge by E20 to 21. In summary, our findings indicate that the structural differentiation of phrenic motoneurons is well-advanced prior to birth and that the descending pathways involved in the control of respiratory function are in place several days before birth.

Animals↗

Photodynamic action of amino substituted hypocrellins: EPR studies on the photogenerations of active oxygen and free radical species.

A novel method has been employed to prepare 2-butylamino-2-demethoxy hypocrellin A (BADMHA) and 2-butylamino-2-demethoxy hypocrellin B (BADMHB). Both compounds exhibit stronger absorption at the phototherapeutic window (600-900 nm). The spin trapping and spin counteraction studies have shown that they are both efficient generators of the active oxygen (1O2, O2*-) in the aerobic condition. Under the anaerobic condition they generate non-oxygen free radical (semiquinone radical anion), and the active oxygen mechanism of photosensitization can be converted into non-oxygen free radical mechanism with the depletion of oxygen. The quantum yields of 1O2 generation of BADMHA and BADMHB are 0.46 and 0.44, respectively. Both are lower than those of their parent compounds HA and HB. But the productions of superoxide anion are enhanced significantly compared with HA and HB, indicating they are both favorable Type I phototherapeutic agents.

Cyclic N-Oxides↗

Transcriptional regulation of RANTES expression in T lymphocytes.

We first identified the RANTES chemokine as part of a search for genes expressed by T lymphocytes "late", 3-5 days, after T-cell activation. The kinetics of expression of RANTES and a small number of other genes are unusual and the mechanism of such delayed expression is unknown. In order to uncover a mechanism for such "late" expression, we identified and characterized the RANTES promoter and a novel transcription factor regulating RANTES expression in T lymphocytes. RANTES factor of late activated T lymphocytes (RFLAT)-1 is a member of the Krüppel-like family of transcription factors. Like RANTES, RFLAT-1 expression is "late" after T-cell activation. But, unlike RANTES, regulation of RFLAT-1 expression appears to be translational rather than transcriptional.

Animals↗

New potential photodynamic therapeutic anti-cancer agents: synthesis and characterization of demethoxy amino-substituted hypocrellins.

A novel method was used to obtain demethoxy amino-substituted hypocrellin derivatives. The reaction condition was mild and amino substitution occurred at position 2 or 11 of hypocrellins with high yield. The photophysical and photochemical properties of the amino-substituted hypocrellins derivatives were investigated, and their significantly enhanced red absorptivities and strong active oxygen-generating functions qualified them as promising photodynamic therapeutic anti-cancer agents.

Antineoplastic Agents↗

Economic and outcomes assessment of magnetic resonance imaging in the evaluation of headache.

We sought to evaluate the economic impact and diagnostic utility of magnetic resonance imaging (MRI) in the management of patients with headache and nonfocal physical examinations. Computerized medical records were retrospectively reviewed of 1,233 patients presenting for MRI of headache at our institution over a 3-year period (1992-1995). Patients with focal findings at physical examination, prior brain surgery, head trauma, or immunocompromise were excluded. A model was developed to assess the cost associated with the MR test results, and actual average institutional costs of performing an examination applied. Correlative statistical analysis of referring specialties and positive tests was also performed. Three hundred twenty-eight patients who met the above criteria were retained in the sample. One hundred sixty-three patients (50%) had negative MR test results. Of the 50% of patients with positive studies, only 5 (1.5%) had clinically significant MR results. The average cost of an MR examination was 517 dollars (1998 dollars). The cost per clinically significant managed case detected was 34,535 dollars. No statistically significant difference was found among referring specialties and clinically significant MR results. Our results indicate that MRI of nonfocal headache yields a low percentage of positive clinically significant results and has limited cost-effectiveness. Referring specialty had no significant bearing on these outcomes, regardless of specialist experience.

Adolescent↗

Development of the rat phrenic nerve and the terminal distribution of phrenic afferents in the cervical cord.

The development of the right phrenic nerve and the distribution of phrenic nerve afferents to the spinal cord have been examined with the aid of electron microscopy and carbocyanine dye retrograde diffusion along the phrenic nerve, respectively. The formation of fascicles in the right phrenic nerve commenced at E15, while Schwann cells penetrated the nerve from E17 and myelination began at P0. The total number of axons in the right phrenic nerve decreased from E15 (943, 965 in two animals) to E19 (539, 582), remained steady until P0 (564, 594) before rising to almost adult values by P7 (689, 934). The postnatal rise in number of axons appears to be due to a large influx of unmyelinated axons. Carbocyanine dye tracing revealed that at E13, neurons in dorsal root ganglia C(2) to C(6) contributed peripheral processes to the phrenic nerve. Phrenic afferents arrived in the spinal cord by E13 and penetrated the dorsal horn at E14. Three terminal fields for phrenic afferents became apparent by E17. These were:(1) in the central parts of laminae I to V, (2) medially in laminae V to VII or adjacent area X near the central canal, (3) in laminae VIII and IX, around the differentiating phrenic motoneurons. Around the time of birth, some phrenic afferents in the second group were distributed across the midline and could be seen to approach the ventromedial dendritic bundle of phrenic motoneurons on the contralateral side, but these were no longer seen by P4. Just before birth (E21), afferents in the third group divided into two further subsets, supplying the dorsolateral and ventromedial groups of phrenic motoneuron dendritic bundles, respectively. Our findings strongly suggest that phrenic afferent differentiation is largely complete by birth.

Afferent Pathways↗

RFLAT-1: a new zinc finger transcription factor that activates RANTES gene expression in T lymphocytes.

RANTES (Regulated upon Activation, Normal T cell Expressed and Secreted) is a chemoattractant cytokine (chemokine) important in the generation of inflammatory infiltrate and human immunodeficiency virus entry into immune cells. RANTES is expressed late (3-5 days) after activation in T lymphocytes. Using expression cloning, we identified the first "late" T lymphocyte associated transcription factor and named it "RANTES Factor of Late Activated T Lymphocytes-1" (RFLAT-1). RFLAT-1 is a novel, phosphorylated, zinc finger transcription factor that is expressed in T cells 3 days after activation, coincident with RANTES expression. While Rel proteins play the dominant role in RANTES gene expression in fibroblasts, RFLAT-1 is a strong transactivator for RANTES in T cells.

Adult↗