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Biomedical subjects

J Tang

Publications and source records attributed to J Tang.

At least 289 records · Page 16Linked to original sources

Synthesis, antiviral activity, and biological properties of vinylacetylene analogs of enviroxime.

A series of vinylacetylene analogs of Enviroxime (1) was synthesized. The new compounds are potent inhibitors of poliovirus in tissue culture. Cross-sensitivity with Enviroxime-derived mutants shows that the new compounds have the same mechanism of action as Enviroxime, which involves the viral 3A protein. In studies with Rhesus monkeys, the p-fluoro derivative 12 was found to be unique in providing oral bioavailability. Metabolism studies using hepatic microsomes suggest that this procedure would be a useful in vitro method for selecting the appropriate animal model for testing oral absorption. Compound 12 was found to be efficacious by oral administration in treating a Coxsackie A21 infection in CD-1 mice.

Animals↗

A novel cytosolic calcium-independent phospholipase A2 contains eight ankyrin motifs.

We report the purification, molecular cloning, and expression of a novel cytosolic calcium-independent phospholipase A2 (iPLA2) from Chinese hamster ovary cells, which lacks extended homology to other phospholipases. iPLA2 is an 85-kDa protein that exists as a multimeric complex of 270-350 kDa with a specific activity of 1 micromol/min/mg. The full-length cDNA clone encodes a 752-amino acid cytoplasmic protein with one lipase motif (GXS465XG) and eight ankyrin repeats. Expression of the cDNA in mammalian cells generates an active 85-kDa protein. Mutagenesis studies show that Ser465 and the ankyrin repeats are required for activity. We demonstrate that iPLA2 selectively hydrolyzes the sn-2 over sn-1 fatty acid by 5-fold for 1,2-dipalmitoyl phosphatidylcholine in a mixed micelle. Moreover, we found the fatty acid preference at the sn-2 position to be highly dependent upon substrate presentation. However, iPLA2 does have a marked preference for 1,2-dipalmitoyl phosphatidic acid presented in a vesicle, generating the lipid second messenger lysophosphatidic acid. Finally the enzyme is able to hydrolyze the acetyl moiety at the sn-2 position of platelet-activating factor.

Amino Acid Sequence↗

Vector-parasite transmission complexes for onchocerciasis in West Africa.

BACKGROUND: In West Africa, there are two strains of the filarial parasite Onchocerca volvulus, which differ in their ability to induce ocular disease. Transmission studies have suggested that six sibling species of the parasite vector, the black fly Simulium damnosum sensu lato, allow development of the two strains of O volvulus with varying efficiency. We aimed to test the hypothesis of parasite-vector complexes, whereby the two parasite strains, known as forest and savanna, are preferentially transmitted by distinct groups of the species of S damnosum S l. METHODS: During 1993 and 1994, wild black flies were collected from 11 river basins within the area covered by the Onchocerciasis Control Programme (OCP). The flies were dissected and filarial larvae, ovaries, and malpighian tubules removed. Genomic DNA was extracted from larvae, and PCR amplification was used to classify O volvulus parasites as forest or savanna strains. PCR-amplified DNA from ovaries and malpighian tubules was used to distinguish sibling species of S damnosum s l. S yahense and S squamosum were distinguished by body colour. FINDINGS: 214 of 105105 flies dissected were infected with filarial larvae; 84 of these were infected with mature O volvulus parasites. Of the 35 savanna-dwelling infected flies. 17 carried forest-strain parasites and 18 savanna-strain parasites. Of the 45 infected flies identified as the forest dwelling sibling species. 20 carried savanna-strain parasites and 25 forest-strain parasites. No significant differences were found in the numbers of mature larvae of each strain carried by the forest-dwelling species of fly or in the number of forest and savanna larvae in savanna-dwelling vector species. INTERPRETATION: Vector-parasite transmission complexes do not currently play a part in the biology of O volvulus transmission in the area of the OCP in West Africa. This finding has important strategic implications for the future of efforts to control onchocerciasis in West Africa.

Africa, Western↗

Morphologic changes in collagen fibers after 830 nm diode laser welding.

BACKGROUND AND OBJECTIVE: The mechanism of laser tissue welding is elusive, but collagen transitions are somehow involved. Collagen fiber modifications observed after 830 nm diode laser welding are presented in this study. STUDY DESIGN/MATERIALS AND METHODS: A 830 nm diode laser assisted longitudinal aortorrhaphy was performed on 37 Wistar rats, with shots of 0.5 W in power, 8 sec in duration and 250 W/cm2 in irradiance. Energy utilized ranged from 400-550 J/ mm2 for 1 cm-length of anastomosis. After laser welding, histological modifications in collagen fibers were observed through optic, scanning electron, and electron microscopic examination. RESULTS: After laser welding, collagen fibers lost a proportion of birefringence. Under electron microscope, the different changes in collagen fibers were visualized being either fused, "roped," swollen, or dissolved, surrounded by normal ones situated in the same zone. CONCLUSION: These data suggest that diode laser heating denatured part of the collagenic fibers, and that these morphologic changes play an important role in laser welding.

Anastomosis, Surgical↗

The use of electron tomography for structural analysis of disordered protein arrays.

A method based on Fourier transforms is described for obtaining a 3-D reconstruction from a paracrystalline object with static disorder. The method is derived from the standard methods used in 3-D reconstruction of 2-D crystals except that all of the Fourier coefficients are used and not just the sampled data from the periodic lattice. Thus, not only is the spatially ordered part of the structure visualized in 3-D, but also the spatially disordered part. Application of the method to 3-D reconstructions Application of the method to 3-D reconstructions of insect flight muscle is described as well as prospects for extension of the method to radiation-sensitive specimens.

Algorithms↗

Effects of ligustrazine on bone marrow microvessel system in the early period of acute radiation injury in mice.

Sublethally irradiated mice were immediately treated with 250 mg/kg Ligustrazine Phosphiatis intraperitoneally twice a day for seven days, and the bone marrow microvessels of the Ligustrazine group was much greater than that of the control group. On the 7th day, the amount of the control group decreased to normal, while the ligustrazine group was still increasing, and the microvessel area was enlarged obviously.. The percentage of the hematopoietic tissue volume in bone marrow between the two groups had no significant difference in the first 7 days. On the 7th day after irradiation, the peripheral neutrophilic granulocytes increased in the Ligustrazine group. The results suggested that early use of Ligustrazine after acute radiation injury might improve the blood supply of bone marrow, and be helpful for recovery of hematopoiesis.

Animals↗

Effect of amlodipine on the growth of vascular smooth muscle cells of spontaneously hypertensive rats.

The effect of anti-hypertensive drug amlodipine on regression of cardiovascular hypertrophy due to hypertension was studied by using cultured smooth muscle cells derived from arteries of spontaneously hypertensive rats (SHR) and measuring [3H]-TdR and [3H]-Leucine binding. 48 h after adding amlodipine, [3H]-TdR binding in arterial smooth muscle cells from SHR in vitro was reduced by 50.5% and [3H]-Leucine binding was reduced by 56.2% as compared with neuropeptide Y (NPY)-treated group. However, there was no significant change in cell number. The results showed that amlodipine could effectively inhibit increase of DNA and protein synthesis of vascular smooth muscle cell (VSMC) due to NPY. It indicates that amlodipine is of great significance on regression of genesis and development of cardiovascular hypertrophy due to hypertension.

Amlodipine↗

The relationship between 67KD laminin receptor expression and metastasis of hepatocellular carcinoma.

The 67KD laminin receptor (LN-R) that binds laminin (LN) is involved in the metastasis cascade. Using immunohistochemical technique, in situ hybridization and reverse transcription polymerase chain reaction (RT-PCR), we studied LN-R protein and RNA levels in 30 cases of human hepatocellular carcinoma (HCC) to further understand its role in the metastasis of HCC. In our 14 cases of HCC with metastasis, its positive rates were 71.4%, 57.1%, 85.7% respectively, whereas its positive expression in 16 cases without metastasis were 31.3%, 18.8%, 50.0% respectively. The significant difference was found between these two groups. The results suggest that the 67KD LN-R expression plays a very important role in the metastasis of HCC.

Basement Membrane↗

Study on the protective effects of compound blood-activating soup on bone marrow hematopoietic cells in acute radiation injured mice.

After irradiation with 8 Gy 60Co gamma-ray, mice were immediately given intraperitoneal injection of 200 mg 100% compound blood-activating soup twice a day. On the 3rd and 7th day, the P53 gene expression of bone marrow hematopoietic cells in Chinese drug group was found to be higher than that in normal group, and it was also significantly higher than that in control group. The expression level of GADD153 gene which was not expressed in normal group was much lower in Chinese drug group than that in control group. On the 7th day after irradiation, the P53 and GADD153 gene expression levels of splenic mononuclear cells were consistent with those of bone marrow hematopoietic cells both in Chinese drug group and control group. On the 3rd and 7th day, the bone marrow hematopoietic tissue volume in Chinese drug group was higher than that in control group, with no difference found between the two groups. While on the 14th day, the difference became significant (P < 0.01). The results showed that commonly used blood-activating and stasis-eliminating drugs may strengthen the viability of hematopoietic cells and promote the rehabilitation of hematopoiesis by inducing wt-P53 expression to block the bone marrow hematopoietic cells in G1 phase, during which DNA could be repaired.

Animals↗

Heteroduplex analysis in medical entomology: A rapid and sensitive sequence-based tool for population and phylogenetic studies.

Classical studies on the insect vectors of parasitic diseases have relied on morphological, biochemical and cytological characters to classify vector species. These are often inadequate for a detailed dissection of the dynamics of the parasite-vector relationship. Molecular techniques have the potential to provide more reliable data on various aspects of vector biology, including population genetics, molecular phylogenetics, and molecular differentiation and classification of closely related species. However, most molecular techniques are expensive, cumbersome or difficult to apply to the analysis of a large number of samples. Here, Jianming Tang and Tom Unnasch discuss the practical advantages of heteroduplex analysis for the study of medically important vectors, using the black flies that serve as vectors for the filarial parasite Onchocerca volvulus as an example. This technique is simple, rapid, inexpensive and capable of detecting minor differences among DNA sequences.

Journal Article↗

Mutational analysis of mitochondrial DNA of children with Rett syndrome.

The present study was undertaken to identify whether mitochondrial DNA (mtDNA) mutations were involved in the pathogenesis of Rett syndrome (RS). Mitochondrial DNA from 15 children with RS and 14 of their mothers was analyzed. No large deletions in mtDNA were found using Southern blot with a full-length mtDNA as a probe. Polymerase chain reaction amplification and single strand conformation polymorphism analysis showed mutations in region 2650-3000 encoding 16S rRNA of mtDNA in 13 cases of RS and 11 of their mothers. DNA sequence analysis and mismatch polymerase chain reaction results revealed a point mutation (C --> T) at position 2835 in 7 cases of RS and 6 of their mothers. The same mutation was not found in a total of 30 normal controls. These data indicate that mtDNA may play an important role in the pathogenesis of RS.

Case-Control Studies↗

Rational design of allosteric ribozymes.

BACKGROUND: Efficient operation of cellular processes relies on the strict control that each cell exerts over its metabolic pathways. Some protein enzymes are subject to allosteric regulation, in which binding sites located apart from the enzyme's active site can specifically recognize effector molecules and alter the catalytic rate of the enzyme via conformational changes. Although RNA also performs chemical reactions, no ribozymes are known to operate as true allosteric enzymes in biological systems. It has recently been established that small-molecule receptors can readily be made of RNA, as demonstrated by the in vitro selection of various RNA aptamers that can specifically bind corresponding ligand molecules. We set out to examine whether the catalytic activity of an existing ribozyme could be brought under the control of an effector molecule by designing conjoined aptamer-ribozyme complexes. RESULTS: By joining an ATP-binding RNA to a self-cleaving ribozyme, we have created the first example of an allosteric ribozyme that has a catalytic rate that can be controlled by ATP. A 180-fold reduction in rate is observed upon addition of either adenosine or ATP, but no inhibition is detected in the presence of dATP or other nucleoside triphosphates. Mutations in the aptamer domain that are expected to eliminate ATP binding or that increase the distance between aptamer and ribozyme domains result in a loss of ATP-specific allosteric control. Using a similar design approach, allosteric hammerhead ribozymes that are activated in the presence of ATP were created and another ribozyme that can be controlled by theophylline was created. CONCLUSIONS: The catalytic features of these conjoined aptamer-ribozyme constructs demonstrate that catalytic RNAs can also be subject to allosteric regulation-a key feature of certain protein enzymes. Moreover, by using simple rational design strategies, it is now possible to engineer new catalytic polynucleotides which have rates that can be tightly and specifically controlled by small effector molecules.

Adenosine↗

Wiskott-Aldrich syndrome protein is associated with the adapter protein Grb2 and the epidermal growth factor receptor in living cells.

Src homology domains [i.e., Src homology domain 2 (SH2) and Src homology domain 3 (SH3)] play a critical role in linking receptor tyrosine kinases to downstream signaling networks. A well-defined function of the SH3-SH2-SH3 adapter Grb2 is to link receptor tyrosine kinases, such as the epidermal growth factor receptor (EGFR), to the p21ras-signaling pathway. Grb2 has also been implicated to play a role in growth factor-regulated actin assembly and receptor endocytosis, although the underlying mechanisms remain unclear. In this study, we show that Grb2 interacts through its SH3 domains with the human Wiskott-Aldrich syndrome protein (WASp), which plays a role in regulation of the actin cytoskeleton. We find that WASp is expressed in a variety of cell types and is exclusively cytoplasmic. Although the N-terminal SH3 domain of Grb2 binds significantly stronger than the C-terminal SH3 domain to WASp, full-length Grb2 shows the strongest binding. Both phosphorylation of WASp and its interaction with Grb2, as well as with another adapter protein Nck, remain constitutive in serum-starved or epidermal growth factor-stimulated cells. WASp coimmunoprecipitates with the activated EGFR after epidermal growth factor stimulation. Purified glutathione S-transferase-full-length-Grb2 fusion protein, but not the individual domains of Grb2, enhances the association of WASp with the EGFR, suggesting that Grb2 mediates the association of WASp with EGFR. This study suggests that Grb2 translocates WASp from the cytoplasm to the plasma membrane and the Grb2-WASp complex may play a role in linking receptor tyrosine kinases to the actin cytoskeleton.

Adaptor Proteins, Signal Transducing↗

Effect of the intensity of transcutaneous acupoint electrical stimulation on the postoperative analgesic requirement.

Given the inherent side effects associated with both opioid and nonopioid analgesic drugs, a nonpharmacologic therapy that could decrease the need for analgesic medication would be valuable. We designed a sham-controlled study to assess the effect of the intensity of transcutaneous acupoint electrical stimulation (TAES) on postoperative patient-controlled analgesia (PCA) requirement for hydromorphone (HM), the incidence of opioid-related side effects, and the recovery profile after lower abdominal surgery. One hundred one healthy consenting women undergoing lower abdominal procedures with a standardized general anesthetic technique were randomly assigned to one of four postoperative analgesic treatment regimens: Group I (n = 26) PCA only; Group II (n = 25), PCA + sham-TAES (no electrical stimulation); Group III (n = 25), PCA + low-TAES (4-5 mA of electrical stimulation); Group IV (n = 25), PCA + high-TAES (9-12 mA of electrical stimulation). The PCA device was programmed to deliver HM, 0.2-0.4 mg intravenously boluses "on demand," with a minimum lockout interval of 10 min. The TAES skin electrodes were placed at the Hegu acupoint on the nondominant hand and on both sides of the surgical incision. The TAES frequency was set in the dense-and-disperse mode, alternating at 2 Hz and 100 Hz every 3 s, with stimulation of the hand and incision alternated every 6 s. The patients in Groups II-IV were instructed to use TAES every 2 h for 30 min while awake. After discontinuation of PCA, oral pain medications were administered on demand. The postoperative PCA-HM requirement, pain scores, opioid-related side effects, and requirements for antiemetic and antipruritic medication were recorded. High-TAES decreased the HM requirement by 65% and reduced the duration of PCA therapy, as well as the incidence of nausea, dizziness, and pruritus. Low-TAES produced a 34% decrease in the HM requirement compared with only 23% in the "sham" TAES group. We conclude that high-TAES produced a significant decrease in the PCA opioid requirement and opioid-related side effects after low intraabdominal surgery.

Abdomen↗

The effect of GP683, an adenosine kinase inhibitor, on the desflurane anesthetic requirement in dogs.

UNLABELLED: The availability of an analgesic compound devoid of the side effects associated with the commonly used opioid and nonsteroidal antiinflammatory drugs would be useful during the perioperative period. Although adenosine has analgesic and anesthetic-sparing properties, it also produces dose-dependent cardiovascular depression. Inhibitors of adenosine kinase may be able to provide analgesia without producing acute cardiovascular or respiratory depression. This preliminary study investigated the effects of a novel adenosine kinase-inhibiting drug, GP683, on the minimum alveolar anesthetic concentration (MAC) of desflurane in dogs. Seven mongrel dogs were administered one of three different GP683 dose regimens (or the solvent) by intravenous infusion on separate occasions according to a cross-over study design. After determining the baseline desflurane MAC value, GP683 was infused at 75, 150, or 300 microg x kg(-1) x min(-1) for 5 min as a loading dose, followed by 15, 30, or 60 microg x kg(-1) x min(-1) for an additional 85 min to maintain a stable plasma drug level. The desflurane MAC was redetermined 30-90 min after starting the study drug or vehicle infusion, and 30-90 min and 120-180 min after termination of the infusion. Cardiovascular variables and plasma concentrations of GP683 were determined at specific intervals before, during, and after the MAC determinations. The three GP683 dose regimens produced 22%, 31%, and 50% decreases in the desflurane MAC, respectively. In addition, there was good correlation between the decrease in desflurane MAC and the plasma GP683 concentration (r = -0.78). Although the mean arterial pressure (MAP) was decreased up to 25% by the highest infusion rate of GP683, adjustments in the desflurane concentration to an equi-MAC value resulted in normalization of the MAP values. Furthermore, GP683 produced no changes in heart rate. In conclusion, the adenosine kinase-inhibiting drug, GP683, produced dose-dependent decreases in the desflurane MAC of dogs without producing untoward hemodynamic changes. IMPLICATIONS: An investigational drug (GP683) that can increase the levels of an important endogenous substance in the body (adenosine) has been found to decrease the anesthetic requirement in dogs without producing adverse effects on the cardiovascular system.

Adenosine Kinase↗

Eltanolone as an alternative to propofol for ambulatory anesthesia.

UNLABELLED: The intravenous (i.v.) steroid anesthetic, eltanolone, compares favorably to propofol with respect to its induction characteristics. This double-blind investigation was designed to compare the induction and recovery profile of eltanolone (versus propofol) when it was used for both induction and maintenance of ambulatory anesthesia. Eighty-three consenting ASA physical status I-III outpatients undergoing minor gynecologic or urologic procedures lasting 10-40 min were randomly assigned to one of three anesthetic treatment groups. All patients received midazolam, 2 mg i.v., and fentanyl, 50 micrograms i.v., before induction of anesthesia. The control group (Group 1) was induced with propofol, 2.4 mg/kg i.v. (18-60 yr or ASA physical status I or II) or 1.6 mg/kg i.v. (61-80 yr and/or ASA physical status III), followed by intermittent bolus doses of 0.6 mg/kg i.v. in combination with N2O 67% for maintenance of anesthesia. In Group 2, anesthesia was induced with eltanolone, 0.75 mg/kg i.v., (18-60 yr and/or ASA physical status I or II) or 0.5 mg/kg i.v. (61-80 yr and/or ASA physical status III), and maintained with intermittent bolus injections of 0.2 mg/kg i.v. and N2O 67%. Group 3 received eltanolone, 1.0 mg/kg i.v. (18-60 yr and/or ASA physical status I or II), or 0.75 mg/kg i.v. (61-80 yr and/or ASA physical status III), followed by intermittent bolus injections of 0.2 mg/kg i.v. and N2O 67%. In addition to recording the induction and recovery times and side effects, psychomotor testing was performed before and at 30-min intervals after anesthesia. Induction times (57 +/- 23, 67 +/- 26, and 61 +/- 22s, respectively) were similar in all three groups. Although eltanolone produced no pain on injection (versus 52% in the propofol group), 10% of the eltanolone-treated patients (versus none in the propofol group) developed transient cutaneous (rash-like) reactions. The total dose of study medication used during the anesthetic period was 9.2 +/- 3.7 mg.kg-1.h-1 in the propofol group compared with 3.3 +/- 1.4 mg.kg-1.h-1 and 3.3 +/- 1.9 mg.kg-1.h-1 in Groups 2 and 3, respectively. Early recovery times were significantly shorter after propofol anesthesia. However, times to ambulation, micturition, and being judged "fit for discharge," as well as recovery of cognitive function, were similar in all three groups. Although ethanolone seems to be a safe and effective i.v. anesthetic, these data suggest that it is unlikely to replace propofol in the ambulatory setting. IMPLICATIONS: Eltanolone is an investigational steroid anesthetic that causes less pain on injection and less cardiovascular depression than propofol (the most widely used intravenous anesthetic in the outpatient setting). Unfortunately, emergence from anesthesia after ambulatory surgery is slower with eltanolone compared with propofol. Therefore, it is unlikely that eltanolone will replace propofol for outpatient anesthesia.

Adult↗