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Biomedical subjects

A H Chang

Publications and source records attributed to A H Chang.

17 recordsLinked to original sources
PubMed2001

Potentiation of opioid analgesia in dopamine2 receptor knock-out mice: evidence for a tonically active anti-opioid system.

Dopamine systems are intimately involved with opioid actions. Pharmacological studies suggest an important modulatory effect of dopamine and its receptors on opioid analgesia. We have now examined these interactions in a knock-out model in which the dopamine(2) (D(2)) receptor has been disrupted. Loss of D(2) receptors enhances, in a dose-dependent manner, the analgesic actions of the mu analgesic morphine, the kappa(1) agonist U50,488H and the kappa(3) analgesic naloxone benzoylhydrazone. The responses to the delta opioid analgesic [d-Pen(2),d-Pen(5)]enkephalin were unaffected in the knock-out animals. Loss of D(2) receptors also potentiated spinal orphanin FQ/nociceptin analgesia. Antisense studies using a probe targeting the D(2) receptor revealed results similar to those observed in the knock-out model. The modulatory actions of D(2) receptors were independent of final sigma receptor systems because the final sigma agonist (+)-pentazocine lowered opioid analgesia in all mice, including the D(2) knock-out group. Thus, dopamine D(2) receptors represent an additional, significant modulatory system that inhibits analgesic responses to mu and kappa opioids.

3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cycloh↗
PubMed2001

Synthetic explorations towards 3-deoxy-3-fluoro derivatives of D-perosamine.

Based on a literature precedent, preparation of methyl 4-azido-3,4,6-trideoxy-3-fluoro-alpha-D-mannopyranoside (18) was attempted via fluorination of methyl 4-azido-2-O-benzyl-4,6-dideoxy-alpha-D-altropyranoside with diethylaminosulfur trifluoride (DAST). Contrary to expectations, the reaction took place with retention of configuration at the site of the fluorination yielding methyl 4-azido-2-O-benzyl-3,4,6-trideoxy-3-fluoro-alpha-D-altropyranoside. Treatment with DAST of methyl 4-azido-2-O-benzyl-4,6-dideoxy-alpha-D-allopyranoside (8), or its 2-(p-methoxybenzyl) analog 9 resulted in fluorination with inversion of configuration at position 3, to give the corresponding 3-deoxy-3-fluoro glucopyranosides 10 and 11, respectively. Accordingly, compound 18 was prepared from 11, by de-p-methoxybenzylation at O-2, followed by inversion of configuration at C-2 in the resulting methyl 4-azido-3,4,6-trideoxy-3-fluoro-alpha-D-glucopyranoside. The 2-O-methyl analog of 18 (19) was prepared by methylation of 18. Compounds 18 and 19 were converted, conventionally, into the 3-fluoro analogs of the terminal determinants of the O-PS of Vibrio cholerae O:1, serotype Inaba and Ogawa, respectively.

Diethylamines↗
PubMed2001

Hck SH3 domain-dependent abrogation of Nef-induced class 1 MHC down-regulation.

The ability of specific virally encoded proteins to down-regulate MHC class I molecules may enable infected cells to elude killing by CTL. In the case of HIV-1, Nef appears to be responsible for this effect. Thus, interfering with Nef-induced MHC class I down-regulation would be a strategy for increasing HIV-1-specific CTL activity, particularly towards long-lived T cell populations such as memory T cells that harbor replication-competent virus. Here, using two Nef-expressing human cell model systems, we show that a dominant-negative mutant derived from the Hck protein-tyrosine kinase, composed of the Hck N-terminal region, as well as the SH3 and SH2 domains, was able to inhibit Nef-induced MHC class I molecule down-regulation. This effect was SH3 domain dependent as it was not evident when the cells were transfected with DN-Hck-W93F, an SH3 domain mutant. The inhibitory effect of dominant-negative-Hck (DN-Hck) on Nef-induced class I down-regulation suggests that this Nef-mediated effect requires an interaction between the Nef polyproline site and an SH3-containing cellular protein that is involved in MHC class I molecule turnover. Interfering with the function of the Nef SH3 binding site in this way represents a strategy for assisting the host CTL response to clear HIV-1-infected cells.

Binding Sites↗
PubMed2000

Practice-related changes in lumbar loading during rapid voluntary pulls made while standing.

OBJECTIVE: To determine if five days of practice on a novel dynamic, multi-joint pulling task resulted in lower magnitudes of lumbar loading or a more consistent relationship between pulling force and lumbar loading. DESIGN: A repeated measures design compared how practice influenced the magnitude of lumbar torque and the correlations between lumbar torque and pulling force. BACKGROUND: Previous studies suggest that practice can decrease the magnitude of lumbar loading on simple manual material handling tasks, but it is unknown whether practice reduces lumbar loading for more complex tasks. Neither is it known whether the consistency of lumbar loading increases with practice. METHODS: Ten healthy adults practiced impulse-like horizontal pulls to targets equaling 20%, 40% and 80% of their estimated maximal dynamic pulling force over 5 days. Movements were unrestrained, other than keeping the feet flat on the ground. We used a four-segment, sagittal plane inverse dynamics model to compute lumbar, hip, knee, and ankle torques on days 1 and 5 from ground reaction forces and moments, pulling forces, and kinematics. RESULTS: An analysis of variance showed significant practice-related changes in lumbar torque at the time of peak pulling force (lumbar torque(peakPF)). The lumbar torque(peakPF) decreased for the 20% pulls, did not change for the 40% pulls, and increased for the 80% pulls. Two subjects showed a significant decrease in lumbar torque(peakPF) for all three force levels. Coefficients of determination between pulling force and lumbar torque (r(2)(PF,LT): a measure of the consistency of the relationship between these two variables) were significantly higher on day 5 than day 1. CONCLUSIONS: Practice on a novel pulling task changed the magnitude of lumbar torques and increased their correlation with pulling force, suggesting that subjects learned strategies that improve motor control of lumbar torques. Relevance The study showed that the magnitude and consistency of lumbar loading changed spontaneously as subjects practiced a novel multijoint pulling task. Such changes may decrease the risk of low-back injury.

Adult↗
PubMed2000

Effect of age on the refractive outcome of myopic photorefractive keratectomy.

PURPOSE: To evaluate the effect of age on the outcome of myopic photorefractive keratectomy (PRK). SETTING: University-based refractive surgery practice. METHODS: A retrospective analysis of 197 eyes that had PRK for myopia was performed. Four groups of patients were compared: Group 1, patients < 30 years (n=35); Group 2, patients 31 to 40 years (n=56); Group 3, patients 41 to 50 year s (n=47); Group 4, patients > 50 years (n=59). The percentage of eyes with an uncorrected visual acuity of 20/20 or better and 20/40 or better and the percentage of eyes with spherical correction within +/-0.5 and +/-1.0 diopter (D) of the attempted correction were derived for each age group. The percentage of patients overcorrected and undercorrected by 1.0 D or more in each age group was also calculated. The difference between the percentage of patients who achieved a visual acuity of 20/20 or better in Group 4 and in the younger groups was statistically significant at 3 months (P =.02) but not at 6 months (P =.70) and 12 months (P =.55). The difference between the percentage of patients who achieved an acuity of 20/40 or better was not significant at any time. The difference between the percentage of patients who were within +/-0.5 D of intended correction in Group 4 and in the younger groups was statistically significant at 3 months (P =.001), 6 months (P =.006), and 12 months (P =.008); the difference between the percentage of patients who were within +/-1.0 D of intended correction was not significant at any time. The difference between the percentage of patients overcorrected and undercorrected by 1.0 D or more in Group 4 and in the younger groups was not significant at any time. In the 3 younger groups, age did not significantly affect visual outcome or predictability. However, there was a significant difference between Group 4 and the 3 younger groups in predictability of the refractive outcome at 3, 6, and 12 months. Age may play a role in the outcome of refractive surgery.

Adolescent↗
PubMed1998

Construction of single-chain antibodies that bind an overlapping epitope of HIV-1 Nef.

The light and heavy chain variable regions of three mouse hybridoma cell lines (AG11, AE6 and EH1) that produce monoclonal antibodies against an overlapping epitope at the C-terminus of Nef were cloned. Sequence analysis of the light and heavy chain variable regions indicated that clones AG11 and AE6, but not EH1, were highly related. Single-chain antibodies were constructed from the cDNA clones of AG11 and EH1, and subcloned into an eukaryotic expressing vector with the green fluorescent protein as marker for expression. Such intracellular antibodies may provide a way in which to inhibit the function of Nef during HIV-1 infection of cells.

Amino Acid Sequence↗
PubMed1997

Spinal analgesic activity of orphanin FQ/nociceptin and its fragments.

Previous work reveals that orphanin FQ/nociceptin (OFQ/N) administered supraspinally produces an initial hyperalgesic response followed by analgesia. Spinally, OFQ/N elicits a rapidly appearing, naltrexone-reversible, dose-dependent analgesia in the tailflick assay without any indication of hyperalgesia. Two OFQ/N fragments, OFQ/N (1-7) and OFQ/N (1-11), are active, but far weaker. Blockade of sigma receptors with haloperidol enhances the analgesic potency of spinal OFQ/N, OFQ/N (1-7) and OFQ/N (1-11), but not as dramatically as supraspinal OFQ. Antisense probes targeting the second and third coding exons, but not the first exon, of the cloned mouse OFQ/N receptor (KOR-3) partially block OFQ/N analgesia.

Analgesics↗
PubMed1996

Inhibition of the self-cleavage reaction of the human hepatitis delta virus ribozyme by antibiotics.

Human hepatitis delta virus (HDV) poses a health threat in populations where chronic hepatitis B is endemic. It is a single-stranded RNA virus of 1700 nucleotides and both genomic and antigenomic sequences contain ribozymes which are important for viral replication. Using ribozyme constructs we show that several classes of antibiotics inhibit the self-cleavage reaction of the HDV ribozyme. Antibiotics of the aminoglycoside, peptide and tetracycline classes all inhibit HDV cleavage in vitro at micromolar concentrations. Neomycin (an aminoglycoside) inhibits HDV self-cleavage with a Ki value of 28 (+/- 10) microM. Neomycin inhibition can be reversed by increasing magnesium ion concentration in a competitive manner. Lead acetate cleaves positions G76, A42 and G28, which surround the ribozyme cleavage site. Both Mg2+ and neomycin prevent lead cleavage. Footprinting experiments using base-specific chemical probes revealed enhanced modifications of a set of bases by neomycin, overlapping with the above mentioned lead cleavages. These observations may indicate that neomycin directly displaces divalent metal ions essential for catalysis.

Anti-Bacterial Agents↗
PubMed1996

Evaluation of a rehabilitative pedorthic: plantar pressure alterations with scaphoid pad application.

Scaphoid or longitudinal arch pads are frequently prescribed pedorthics for foot and ankle rehabilitation. These pedorthics are reported to be effective in mechanically supporting the medial longitudinal arch while reducing plantar and medial soft tissue strain. The objective of this study was to measure alterations in ambulatory plantar pressure metrics in a group of adults secondary to scaphoid pad application. The biomechanical rationale of this study was that the geometry of foot contact would be altered secondary to foot inversion. Ten adult male subjects with biomechanically normal feet were evaluated during multiple trials. A Holter type microprocessor-based portable in-shoe plantar pressure data acquisition system was used to record the dynamic data. Pressures were recorded from eight discrete plantar locations at the hindfoot, midfoot, and forefoot regions of the insole. Statistically significant (p < or = 0.05) increases in peak pressures were seen laterally with scaphoid pad application, while significant decreases in peak pressures with pad usage occurred at the hallux and the calcaneal region of the foot. At the medial longitudinal arch, peak pressures increased from near 0 to 115.3 kPa, contact durations increased from near 0 to 438 ms, and pressure-time integrals increased from near 0 to 33.4 kPa.s.

Adult↗
PubMed1994

Multistep measurement of plantar pressure alterations using metatarsal pads.

Metatarsal pads are frequently prescribed for nonoperative management of metatarsalgia due to various etiologies. When appropriately placed, they are effective in reducing pressures under the metatarsal heads on the plantar surface of the foot. Despite the positive clinical reports that have been cited, there are no quantitative studies documenting the load redistribution effects of these pads during multiple step usage within the shoe environment. The objective of this study was to assess changes in plantar pressure metrics resulting from pad use. Ten normal adult male subjects were tested during a series of 400-step trials. Pressures were recorded from eight discrete plantar locations at the hindfoot, midfoot, and forefoot regions of the insole. Significant increases in peak pressures, contact durations, and pressure-time integrals were noted at the metatarsal shaft region with pad use (P < or = .05). Statistically significant changes in metric values were not seen at the other plantar locations, although metatarsal pad use resulted in mild decreases in mean peak pressures at the first and second metatarsal heads and slight increases laterally. Contact durations decreased at all metatarsal head locations, while pressure-time integrals decreased at the first, second, third, and fourth metatarsal heads. A slight increase in pressure-time integrals was seen at the fifth metatarsal head. The redistribution of plantar pressures tended to relate not only to the dimensions of the metatarsal pads, but also to foot size, anatomic foot configuration, and pad location. Knowledge of these parameters, along with careful control of pad dimensions and placement, allows use of the metatarsal pad as an effective orthotic device for redistributing forefoot plantar pressures.

Adult↗
PubMed1994

[Ender nailing of humeral shaft fractures].

From March 1991 to June 1992, thirteen patients with humeral shaft fracture were managed at our hospital with closed reduction and internal fixation with Ender nails. These patients were mainly victims of traffic accidents and falls and had fractures, head injuries, and chest trauma. The follow-up period was more than 1 year. Operations were performed under C-arm guide and, according to the method of Hall and Pankovich, divided into antegrade and retrograde methods. The average operation time was 104 minutes, ranging from 70 to 160 minutes, and blood loss was less than 100 ml. Twelve patients were available for follow-up with 11 unions (91.6%), and the functional results were satisfactory. Complications included 2 nails backing out and one iatrogenic fracture. There was no infection and no radial nerve injury. We concluded that for those humeral shaft fractures with surgical indication, Ender nailing was a good choice. The advantages include a simple procedure, lower infection rate and less nonunions.

Adult↗
PubMed1992

Detection of staphylococcal enterotoxin B among toxic shock syndrome (TSS)- and non-TSS-associated Staphylococcus aureus isolates.

The association between staphylococcal enterotoxin (SE) B and toxic shock syndrome (TSS) toxin 1 (TSST-1) in menstrual and nonmenstrual TSS was examined. Production of SEB and TSST-1 in the culture supernatants from 344 Staphylococcus aureus isolates was quantitated by noncompetitive ELISA (lower detection limit, 0.5 ng/mL for both assays). In the ELISA for SEB, cross-reactive antibodies to SEC were removed by absorption in a biotin-streptavidin-agarose column (SEC1 at concentrations to 100,000 ng/mL could not be detected). Among TSST-1-negative isolates, SEB production in nonmenstrual TSS isolates (8/13, 62%) was more prevalent than that in either menstrual TSS isolates (1/4; P = .3), non-TSS infections (15/103, 15%; P less than .001), or asymptomatic carriers (14/105, 13%; P less than .001). Expression of SEB and TSST-1 was usually mutually exclusive (only 1.5% of 344 isolates produced both SEB and TSST-1). Multilocus enzyme electrophoretic typing (ET) suggested a clonal origin for both SEB-(55% of ET-5) and TSST-1 (76% of ET-19)-producing isolates. Thus, SEB may be an important cause in TSS where TSST-1 is not elaborated, especially in nonmenstrual TSS isolates.

Enterotoxins↗
PubMed1992

Induction of tumor necrosis factor and interleukin-1 by purified staphylococcal toxic shock syndrome toxin 1 requires the presence of both monocytes and T lymphocytes.

Highly purified staphylococcal toxic shock syndrome toxin 1 (TSST-1) was tested for its ability to induce the cytokines tumor necrosis factor (TNF) and interleukin-1 (IL-1) from fractionated human peripheral blood mononuclear cells prepared from seven healthy donors. Highly purified monocytes alone or T lymphocytes alone did not produce TNF or IL-1 when incubated with TSST-1 at 37 degrees C for up to 72 h. However, the addition of 10 micrograms of TSST-1 per ml to a 1:1 mixture of monocytes and T cells resulted in significant TNF (predominantly TNF-alpha) and IL-1 beta production after 24 h at 37 degrees C. The nature of the monocyte/T-cell interaction did not appear to involve gamma interferon (IFN-gamma), since 10 micrograms of rabbit anti-IFN-gamma per ml did not neutralize TNF-alpha production after TSST-1 induction. Similarly, L243, a monoclonal antibody to HLA-DR which blocks TSST-1 binding to monocytes, did not inhibit TNF-alpha production following TSST-1 induction. However, direct contact between monocytes and T cells was required, since physical separation of cells in double-chamber culture wells abolished TNF-alpha secretion after TSST-1 stimulation. Furthermore, paraformaldehyde fixation of either monocytes or T cells prior to addition to viable T cells or monocytes, respectively, also abolished TNF-alpha secretion, suggesting that aside from cell contact, soluble factors were also involved. Our results suggest that cytokine production involves more than binding of TSST-1 to its receptor on monocytes alone and that cell contact with T cells and the release of a soluble factor(s) other than IFN-gamma may be essential for the induction of cytokines by this toxin.

Anti-Infective Agents, Local↗
PubMedDate not supplied

Ectopic cerebellum presenting as a suprasellar mass in infancy: implications for cerebellar development.

A 4-month-old infant with a history of nasopharyngeal teratoma developed progressive optic neuropathy. Neuroimaging studies demonstrated a solid, isointense, suprasellar mass impinging on optic nerves and chiasm superiorly. The mass was subtotally resected. No attachment of the mass to brain stem or cerebellar structures was noted. Histological examination identified the tissue as developing cerebellum. The cytoarchitecture and cellular constituents of the cerebellar tissue were only slightly distorted. All cerebellar cortical constituents were arranged anatomically, and an external granular cell layer was present superficially. The latter was actively proliferating and appropriately cellular for the infant's age. The clinical presentation of ectopic cerebellum as a suprasellar mass in an infant is highly unusual. Moreover, this example illustrates the ability of cerebellar tissue to mature appropriately in a site distant from the posterior fossa, removed from ascending and descending afferent projections. Intrinsic signaling mechanisms appear sufficient to direct histogenesis in developing cerebellar cortex.

Cerebellar Neoplasms↗