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Biomedical subjects

J Shi

Publications and source records attributed to J Shi.

At least 181 records · Page 10Linked to original sources

The distribution of substance P receptor (NK1)-like immunoreactive neurons in the newborn and adult human spinal cord.

Substance P receptor (i.e. NK1)-like immunoreactive (SPR-LI) neurons were observed in the newborn and adult human spinal cord. Substance P receptor-like immunoreactive neuronal cell bodies were seen most frequently in lamina I, and were scattered throughout the remaining laminae of the dorsal horn and the area around the central canal. Some neurons in the intermediolateral nucleus also showed weak immunoreactivity. The pattern of distribution of SPR-LI neurons in the adult spinal cord was essentially the same as that in the newborn spinal cord. However, SPR-LI neurons cell bodies were seen much more frequently in the newborn than in the adult dorsal horn, especially in lamina II.

Adult↗

A single amino acid change (substitution of glutamate 3 with alanine) in the N-terminal region of rat liver carnitine palmitoyltransferase I abolishes malonyl-CoA inhibition and high affinity binding.

We have recently shown by deletion mutation analysis that the conserved first 18 N-terminal amino acid residues of rat liver carnitine palmitoyltransferase I (L-CPTI) are essential for malonyl-CoA inhibition and binding (Shi, J., Zhu, H., Arvidson, D. N. , Cregg, J. M., and Woldegiorgis, G. (1998) Biochemistry 37, 11033-11038). To identify specific residue(s) involved in malonyl-CoA binding and inhibition of L-CPTI, we constructed two more deletion mutants, Delta12 and Delta6, and three substitution mutations within the conserved first six amino acid residues. Mutant L-CPTI, lacking either the first six N-terminal amino acid residues or with a change of glutamic acid 3 to alanine, was expressed at steady-state levels similar to wild type and had near wild type catalytic activity. However, malonyl-CoA inhibition of these mutant enzymes was reduced 100-fold, and high affinity malonyl-CoA binding was lost. A mutant L-CPTI with a change of histidine 5 to alanine caused only partial loss of malonyl-CoA inhibition, whereas a mutant L-CPTI with a change of glutamine 6 to alanine had wild type properties. These results demonstrate that glutamic acid 3 and histidine 5 are necessary for malonyl-CoA binding and inhibition of L-CPTI by malonyl-CoA but are not required for catalysis.

Alanine↗

[Study on standards for safe and health-protective zone in firework plant].

A retrospective investigation on technology and situation in the production of fireworks, the cause and hazard consequences of accidents in blossom firework enterprises was carried out. The risk factors and their origins, the potential effects on surrounding environments and residents, the manufacture processes producing special potential energy in these enterprises were summarized and assessed. In addition, the consequences of explosive fire accidents were assessed retrospectively by the principle of explosion mechanics and Hopkinson Scaling Law. The safe and health-protective zone of the blossom firework plant was suggested.

Industry↗

Synthesis and biological evaluation of 2',3'-didehydro-2',3'- dideoxy-5-fluorocytidine (D4FC) analogues: discovery of carbocyclic nucleoside triphosphates with potent inhibitory activity against HIV-1 reverse transcriptase.

The discovery of a novel cytosine nucleoside, beta-D-2', 3'-didehydro-2',3'-dideoxy-5-fluorocytidine (D-D4FC), as a potent antihuman immunodeficiency virus (HIV) agent led us to synthesize a series of analogues and derivatives of beta-D-D4FC that could be more selective and also possess increased glycosidic bond stability. The synthesized D-D4FC analogues were evaluated for anti-HIV-1 activity, anticancer activity, and cytotoxicity in various cells. The biological data demonstrated that the 5-substitution of beta-D-D4FC with bromine (6c) and iodine (6d) resulted in the loss of antiviral activity, and the alpha-D anomer (7a) of D-D4FC was also devoid of activity. The 5-fluorouracil analogues (6b and 7b) of D-D4FC were less potent and more cytotoxic than the parent compound, whereas the beta-L-D4FU (11) showed both potent anti-HIV-1 activity and cytotoxicity. N4- and 5'-O-acyl derivatives (17, 15a-c) of beta-D-D4FC exhibited comparable antiviral activity to beta-D-D4FC. In contrast, the N4-isopropyl derivative (20) of beta-D-D4FC was not active against HIV-1, even at 100 microM. The carbocyclic analogues (26a,b) of D4FC demonstrated weak activity against HIV-1 and no toxicity in various cells. The triphosphates (27a,b) of the carbocyclic nucleosides demonstrated potent inhibitory activity against recombinant HIV-1 reverse transcriptase at submicromolar concentrations. Of the compounds tested as potential anticancer agents, beta-D-, alpha-D-, and beta-L-D4FU (6b, 7b, 11) showed inhibitory activity against rat glioma and modest activity against human lung carcinoma, lymphoblastoid, and skin melanoma cells.

Animals↗

Identification of tyrosine phosphorylation sites in the CD28 cytoplasmic domain and their role in the costimulation of Jurkat T cells.

The cytoplasmic domain of CD28 contains four tyrosine residues. Because signal transduction by CD28 appears to involve its tyrosine phosphorylation, we determined sites of CD28 tyrosine phosphorylation using mutants of mouse CD28 that retained tyrosine at one position, with the remaining three positions mutated to phenylalanine. When expressed in Jurkat cells and stimulated by mAb, only the mutants with tyrosine at position 170 or 188 were tyrosine phosphorylated. Phosphorylation of Tyr170 recruits phosphatidylinositol 3-kinase to CD28. Tyr188 has not been associated with any specific signaling event, but we found that ligation of CD28 by the natural ligand B7.2 also induced phosphorylation of Tyr188, suggesting that this event is of physiological importance. Consistent with that possibility, mutation of Tyr188 to phenylalanine severely impaired the ability of mouse CD28 to deliver a costimulus for the expression of CD69 and the production of IL-2. The functional consequences of the mutation of Tyr188 were unique; mutation of the other three tyrosines, individually or in combination, did not impair costimulation. Therefore, of the four CD28 tyrosine residues only Tyr188 is required for signaling in Jurkat cells, suggesting that its phosphorylation is a key event in the costimulation of T cells.

Animals↗

Pharmacokinetic, pharmacodynamic, and safety evaluation of an accelerated dose titration regimen of sotalol in healthy middle-aged subjects.

BACKGROUND: Current labeling recommends that therapy with sotalol be initiated in a monitored setting at 80 mg every 12 hours for 2 to 3 days, followed by 120 to 160 mg every 12 hours for at least 2 days before safety and efficacy can be ascertained and patients discharged. An accelerated titration regimen that shortens hospital stay without compromising patient safety would improve the usefulness of the drug. Although such regimens have been used by clinicians, they have not been formally evaluated. METHODS: Healthy, middle-aged sedentary men and women received sotalol in a double-blind, two-way crossover study with a 2-week washout phase to evaluate an accelerated titration regimen--placebo every 6 hours for four doses, followed by 80 mg sotalol every 6 hours for four doses, then 160 mg sotalol every 12 hours for nine doses--and compare it with the standard titration--placebo alternating with 80 mg sotalol every 6 hours for eight doses, followed by 160 mg sotalol every 12 hours for nine doses. QT intervals, RR intervals, and sotalol concentrations in plasma were measured at specific times throughout the study and during washout in a similar fashion for both regimens. RESULTS: Thirty-four subjects completed both regimens. The target prolongation of QTc (90% of the value achieved at steady state) was achieved 22 1/2 hours sooner with the accelerated titration regimen (P = .0003). There were no cardiovascular adverse events during either loading phase. At no time during the accelerated titration regimen did the sotalol concentrations in plasma or the QTc or RR interval prolongation exceed the values eventually achieved at steady state. The relationship between sotalol concentration and QTc was linear and independent of the regimen. CONCLUSION: The accelerated titration regimen for sotalol can shorten the time to attain the dosage usually required to effectively control arrhythmias, without excessive QT prolongation and the associated increased risk of torsades de pointes. The hospital stay of patients in whom antiarrhythmic therapy with sotalol is initiated can be shortened by 1 day if this accelerated titration regimen is used.

Adrenergic beta-Antagonists↗

Cavernous hemangiomas in the cavernous sinus. Case reports.

BACKGROUND: Extra-axial cavernous hemangiomas are rare and have a propensity to develop within the cavernous sinus. Total removal of these vascular tumors is difficult due to the risk of severe intraoperative bleeding and the complicated neurovascular structures of the cavernous sinus. Only a small number of cases have been reported to be successfully totally removed. METHODS: Retrospective studies were done in three cases of extraaxial cavernous hemangiomas located in the cavernous sinus. All three patients presented with clinical symptoms common to other tumors located in the region, such as headache and impairment of cranial nerve function. Their preoperative MRI results showed significant hyperintensity on T2-weighted images and marked enhancement with gadolinium-DTPA that delineated a sharp tumor margin. RESULTS: All three patients underwent total tumor removal, with an uneventful postoperative course. There was no postoperative neurological deficit in one patient, and a complete ophthalmoplegia and diminished sensation in the V1 distribution in two patients. Three months after operation, follow-up MRI or CT scan showed no residual tumor. CONCLUSION: Surgical resection of these lesions was possible but difficult because of severe bleeding. Avoiding piecemeal removal before the main feeding arteries are interrupted can minimize intraoperative bleeding.

Adult↗

Mechanistic studies show that (-)-FTC-TP is a better inhibitor of HIV-1 reverse transcriptase than 3TC-TP.

Of all of the nucleoside inhibitors approved by the FDA for treatment of AIDS, (-)-beta-2',3'-dideoxy-3'-thiacytidine (3TC, lamivudine) is the only one with the unnatural (-)-beta-L configuration. The fluorinated derivative (-)-beta-2', 3'-dideoxy-5-fluoro-3'-thiacytidine [(-)-FTC] and its triphosphate form have also been reported to have excellent antiretroviral activity against HIV-1 reverse transcriptase (RT). Preliminary results of clinical trials suggest that (-)-FTC is 6- to 10-fold more potent than 3TC. However, the molecular mechanism for the observed enhanced clinical potency of (-)-FTC to inhibit viral replication is not understood. The present mechanistic studies used a transient kinetic approach and were designed to compare the incorporation of 3TC-TP and (-)-FTC-TP into DNA by HIV-1 RT and illuminate key features that may play a role in the differential potency. Here we show that (-)-FTC-TP is incorporated 10-fold more efficiently than 3TC-TP during HIV-1 RT-catalyzed RNA-dependent DNA synthesis. The enhanced incorporation efficiency of (-)-FTC-TP may be a key mechanistic feature that, in part, is responsible for the enhanced potency of (-)-FTC observed in ongoing clinical trials.

Base Sequence↗

Cavernous hemangiomas in the cavernous sinus.

OBJECTIVE: Cavernous hemangiomas located within the cavernous sinus are rare vascular tumors that are very difficult to remove because of severe intraoperative bleeding. The purpose of this study was to analyze the clinical, neuroimaging, and pathological features and the surgical treatment of these tumors. METHODS: Ten patients with cavernous hemangiomas in the cavernous sinus who were surgically treated from August 1985 to October 1997, in our hospital, were retrospectively studied. RESULTS: Among the 10 patients, total tumor removal was performed in four cases, partial removal in two cases, and tumor biopsies in four cases. The four patients who underwent total tumor removal experienced uneventful postoperative courses, with no postoperative neurological deficits for one patient, no new neurological deficits for two patients, and complete ophthalmoplegia and diminished sensation in the distribution of Cranial Nerve V1 for one patient. The two patients who underwent partial removal developed complete ophthalmoplegia and diminished sensation in the distribution of Cranial Nerve V1 after surgery, and one of them experienced contralateral paralysis. All four patients who underwent tumor biopsies experienced severe intraoperative tumor bleeding; one exhibited Cranial Nerve III, IV, and VI injuries after surgery. CONCLUSION: The features of prominent hyperintensity in T2-weighted scans, with well-defined borders in enhancing magnetic resonance imaging scans, or marked enhancement in computed tomographic and magnetic resonance imaging scans, with no tumor blush in angiographic analyses, facilitate the diagnosis of these tumors. These tumors can be divided into two subgroups on the basis of intraoperative findings and pathological features. We do not recommend division and piecemeal removal of the tumor during surgery if the main supplies of the tumor have not been interrupted.

Adult↗

Molecular theory of HexB-SmA-isotropic transitions in ultrathin liquid crystal films.

A microscopic theory is developed to treat the ultrathin film of liquid crystals of molecules that have no cylindrical symmetry. The Hamiltonian is derived from the basic electrostatic interaction among electrons by considering the dipole-dipole and dipole-quadrupole interactions between nonchiral molecules. It exhibits the in-plane sixfold symmetry. From a unified model with the same interaction constants we are able to explain simultaneously the layer-thinning SmA-I transition, the anomalous multiplex heat capacity, the strong singularity in the HexB-SmA transition, and the coexistence of different phases. The theoretical calculations agree quantitatively with recent experimental results for the free-standing 54COOBC films.

Journal Article↗

Novel protein kinases associated with calcineurin B-like calcium sensors in Arabidopsis.

Members of the Arabidopsis calcineurin B-like Ca(2)+ binding protein (AtCBL) family are differentially regulated by stress conditions. One AtCBL plays a role in salt stress; another is implicated in response to other stress signals, including drought, cold, and wounding. In this study, we identified a group of novel protein kinases specifically associated with AtCBL-type Ca(2)+ sensors. In addition to a typical protein kinase domain, they all contain a unique C-terminal region that is both required and sufficient for interaction with the AtCBL-type but not calmodulin-type Ca(2)+ binding proteins from plants. Interactions between the kinases and AtCBLs require micromolar concentrations of Ca(2)+, suggesting that increases in cellular Ca(2)+ concentrations may trigger the formation of AtCBL-kinase complexes in vivo. Unlike most serine/threonine kinases, the AtCBL-interacting kinase efficiently uses Mn(2)+ to Mg(2)+ as a cofactor and may function as a Mn(2)+ binding protein in the cell. These findings link a new type of Ca(2)+ sensors to a group of novel protein kinases, providing the molecular basis for a unique Ca(2)+ signaling machinery in plant cells.

Amino Acid Sequence↗

Pharmacokinetics of the antiviral agent beta-D-2',3'-didehydro-2',3'-dideoxy-5-fluorocytidine in rhesus monkeys.

The values of the pharmacokinetic parameters of the nucleoside antiretroviral agent beta-D-2',3'-didehydro-2',3'-dideoxy-5-fluorocytidine (D-D4FC) in rhesus monkeys were determined with a two-compartment model after the administration of a single dose. The average values for the terminal half-life, renal clearance, and total systemic clearance for the intravenous administration route were 3.6 h and 0.31 and 0.43 liter.kg-1.h-1, respectively. The oral bioavailability of D-D4FC averaged 41%. For the intravenous administration route, 76% of the compound was recovered intact in the urine within 8 h, indicating that D-D4FC was eliminated mainly by renal excretion. D-D4FC was detected in the cerebrospinal fluid (CSF) at similar concentrations after administration by both the intravenous and oral routes. D-D4FC levels in plasma and CSF were higher than the median effective concentration for human immunodeficiency virus type 1 in vitro.

Animals↗

Porcine epithelial beta-defensin 1 is expressed in the dorsal tongue at antimicrobial concentrations.

Epithelial cells and phagocytes contain antimicrobial polypeptides that participate in innate host defense. A recently cloned porcine beta-defensin, PBD-1, was detected by Northern organ blots exclusively in the tongue epithelium. We generated recombinant PBD-1 peptide by using a baculovirus-insect cell expression system and obtained two forms (PBD-142 and PBD-138), which differed by N-terminal truncation. Only PBD-142 was found in scrapings of the surface of the dorsal tongue or the buccal mucosa. Immunohistochemical staining with antibody to PBD-142 revealed that PBD-1 was highly concentrated in an approximately 0.1-mm-thick layer in the cornified tips of the filiform (but not fungiform) papillae of the dorsal tongue and in the superficial squamous cell layers of the buccal mucosa. By scraping, extraction, and semiquantitative Western blotting, the concentration of PBD-1 in the dorsal tongue surface and the buccal mucosa was estimated at 20 to 100 micrograms/ml. PBD-1 had antibacterial activity against Escherichia coli, Salmonella typhimurium, Listeria monocytogenes, and Candida albicans in 10 mM sodium phosphate buffer (pH 7.4). Added NaCl progressively inhibited the activity of PBD-1 against E. coli and C. albicans. In 10 mM sodium phosphate with 125 mM NaCl, the combinations of sublethal concentrations of PBD-1 and the porcine neutrophil peptide PG-3, PR-39, or PR-26 showed synergistic activity against E. coli or the multidrug-resistant S. typhimurium DT104. At its physiologic concentration, PBD-1 has antimicrobial effects under both low- and high-salt conditions encountered in the oral cavity and may contribute to the antimicrobial barrier properties of the dorsal tongue and oral epithelium.

Amino Acid Sequence↗

Use patterns for antipsychotic medications in medicaid patients with schizophrenia.

OBJECTIVE: We investigated the use patterns for antipsychotic medications generated by Medicaid patients with schizophrenia. METHOD: Paid claims data from the California Medicaid program (Medi-Cal) were used to identify 2655 patients with schizophrenia. Data from 1987-1996 were used, during which time Medi-Cal maintained prior authorization restrictions on second generation antipsychotic drugs. Prescription records were used to identify 3 patterns of antipsychotic drug use: no drug therapy for over 1 year; delayed onset of antipsychotic drug therapy; and switches in antipsychotic drugs within 1 year. Multiple logistic regression models were used to identify factors affecting these antipsychotic drug use patterns. RESULTS: Conventional antipsychotic medications account for over 98% of all patient treatment episodes. Over 24% of patients with schizophrenia do not use any antipsychotic medication for periods lasting up to 1 year. Over 24% of treated patients delayed the use of antipsychotic medications at least 30 days. For those patients who did not delay their use of antipsychotic medications, over 47% switched or augmented their initial antipsychotic medication during the first treatment year. Only 11.6% of treated patients achieved 1 year of uninterrupted antipsychotic drug therapy. The mean duration of uninterrupted therapy was 142 days. DISCUSSION: Antipsychotic drug use patterns suggest that conventional antipsychotic medications do not meet the therapeutic needs of patients with schizophrenia.

Ambulatory Care↗

[Protection of spinal motorneurons of section sciatic nerve by transplantation of NT-4 genetically expression cells into the side of section].

The NT-4 genetically engineered cells were made by infecting L-6TG cell (a rat myoblast cell line) in vitro with a retroviral vector pN2A containing the rat NT-4 cDNA. The bioactivities were determined by bioassay of PC12 cell survival rate. The rat with left sciatic nerve transaction was used as a model for treatment by implanting NT-4 genetically modified cell. The condition of motorneurons was assessed by Nissl stain and ChE stain. The results showed that: (1) the percentage of surviving Nissl-stained neurons on the lessened side of NT-4 (+) grafts significantly increased as compared to that with NT-4 (-) grafts 2-3 weeks and 3 months after sciatic nerve transaction, and (2) the grafted cells produced significant increase in the positive ChE stained area after sciatic nerve transaction in 1-3 weeks. Our observations indicate that adult motor neurons are still able to respond to neurotrophic factors and they may require the factors for survival.

Animals↗

[Gene expression of growth factors and their receptors in healing of partial thickness burn wound in rats].

OBJECTIVE: To investigate the role of growth factors and their receptors in partial-thickness burn wound healing. METHODS: SD rats were used. After 10% total body surface area partial-thickness burn, wound tissues were harvested on postburn days (PBDs) 0(normal control), 1, 3, 5, 7, 10 and 14 respectively. The gene expressions of growth factors and their receptors were determined in wound by in situ hybridization and slot blotting hybridization. At the same time, the process of the wound healing was observed histologically, and the regeneration cycle of epidermal cells and the temporal change in inflammatory cells were measured. RESULTS: Inflammatory cells infiltrated into wound surface were neutrophils, followed by macrophages and lastly lymphocytes. Epidermal cells proliferated most actively on PBD 3 and the mitoses of them increased significantly on day 7 after burn. The gene expression of PDGF, PDGFR and EGFR reached peaks on PBD 1 and the gene expression of EGF and TGF beta-R2 were highest on PBD 3. In addition, the gene expression of TGF beta-R1 and TGF beta 1 increased significantly on PBDs 5 and 7 respectively. CONCLUSION: The data suggested that burn can induce gene expression of EGF, PDGF, TGF-beta 1 and their receptors temporally, spatially, and reversibility, which might play a major role in burn wound healing, and the mutual regulation may exist in the gene expression and the cell cycle.

Animals↗

Dose-effect of dietary L-arginine supplementation on burn wound healing in rats.

OBJECTIVE: To investigate the dose-effect of dietary L-arginine supplementation on burn wound healing in rats. METHODS: 218 Sprague-Dawley rats (weighing 200-250 g) were subjected to 10% deep partial thickness scald burns and were randomized into six groups. Groups A, B, C, D, E and F received 800, 400, 200, 100, 50 and 0 mg.kg-1.d-1 L-arginine in the form of L-arginine solution, and 0, 727, 1090, 1272, 1364, and 1454 mg.kg-1.d-1 glycine, respectively. Each solution was isonitrogenous. The times of completing re-epithelization were recorded. The contents of hydroxyproline (OHP) in burn wound area (index of reparative collagen synthesis) and the ratios of type I and type III collagen were examined in all groups. RESULTS: The times of completing re-epithelization (day) in groups A, B, C, D, E, and F were 24.9 +/- 1.95, 22.5 +/- 2.0, 20.2 +/- 2.4, 23.5 +/- 2.6, 23.8 +/- 3.5, and 24.7 +/- 2.3, respectively. The contents of hydroxyproline in groups B, C and D were higher than in groups A, E and F on PBD 7, 10 and 14. The ratios of type I and type III collagen in groups B, C and D were lower than in groups A, E and F. CONCLUSION: Oral dietary L-arginine supplementation from 100 mg.kg-1.d-1 to 400 mg.kg-1.d-1 shortened the times of re-epithelization, increased amounts of hydroxyproline, and accelerated the synthesis of reparative collagen in burn rats.

Animals↗

[The effects of basic fibroblast growth factor on proliferation and differentiation of human dental pulp cells in vitro].

OBJECTIVE: To evaluate the effects of human basic fibroblast growth factor (hbFGF) on proliferation and differentiation of human dental pulp cells in vitro. METHODS: The syntheses of DNA, collagen, fibronection (FN), alkaline phosphatase (ALP) and bone morphogenetic protein (BMP), and the expression of agglutinin were measured with imagine processing and analysis system. RESULTS: hbFGF at concentration of 1-10 micrograms/L stimulated the cell proliferation measured by MTT colorimetric assay, and promoted incorporation of 3H-thymidine at 1-100 micrograms/L. The expression of type I collagen, FN, Con A receptor, and ALP significantly increased at hbFGF concentration of 10-1,000 micrograms/L, but the expression of type III collagen and WGA receptor markedly decreased at the same concentration. There was no significant difference in expression of BMP. CONCLUSION: bFGF has the capability to promote the differentiation of dental pulp cells to odontoblasts in culture.

Alkaline Phosphatase↗