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Biomedical subjects

K Jiang

Publications and source records attributed to K Jiang.

At least 37 records · Page 2Linked to original sources

The phosphoinositide 3-OH kinase/AKT2 pathway as a critical target for farnesyltransferase inhibitor-induced apoptosis.

Farnesyltransferase inhibitors (FTIs) represent a novel class of anticancer drugs that exhibit a remarkable ability to inhibit malignant transformation without toxicity to normal cells. However, the mechanism by which FTIs inhibit tumor growth is not well understood. Here, we demonstrate that FTI-277 inhibits phosphatidylinositol 3-OH kinase (PI 3-kinase)/AKT2-mediated growth factor- and adhesion-dependent survival pathways and induces apoptosis in human cancer cells that overexpress AKT2. Furthermore, overexpression of AKT2, but not oncogenic H-Ras, sensitizes NIH 3T3 cells to FTI-277, and a high serum level prevents FTI-277-induced apoptosis in H-Ras- but not AKT2-transformed NIH 3T3 cells. A constitutively active form of AKT2 rescues human cancer cells from FTI-277-induced apoptosis. FTI-277 inhibits insulin-like growth factor 1-induced PI 3-kinase and AKT2 activation and subsequent phosphorylation of the proapoptotic protein BAD. Integrin-dependent activation of AKT2 is also blocked by FTI-277. Thus, a mechanism for FTI inhibition of human tumor growth is by inducing apoptosis through inhibition of PI 3-kinase/AKT2-mediated cell survival and adhesion pathway.

Alkyl and Aryl Transferases↗

[The identification and cloning of human ubiquitin binding enzyme cDNA].

OBJECTIVE: To identify and clone the gene encoding human ubiquitin binding enzyme and study its expression spectrum. METHODS: According to the sequence of human EST, which is highly homologous to the mouse ubiquitin conjugating enzyme (E2), primers used for library screening were synthesized to screen the human fetal brain cDNA library. The gene was analyzed by making use of bioinformatics and its expression spectrum was studied by using multiple-tissue Northern blot. RESULTS: Two cDNA clones encoding human ubiquitin conjugating enzyme were isolated and identified. Both containing the ubiquitin conjugating domain, they were 88% identical in amino acid sequences and found to be isoforms of each other with only an exon excised from the short sequence. They belonged to a highly conserved, and widely expressed E2 enzyme family. Northern blot showed that they were expressed exclusively in heart, placenta, and pancreas while no transcripts could be detected in brain, lung, liver, skeletal muscle, or kidney. CONCLUSIONS: The gene encoding human ubiquitin binding enzyme is expressed under both temporal and spatial control. As a key enzyme in the degradation of proteins, ubiquitin conjugating enzymes play a central role in the expression regulation on the level of post-translation.

Amino Acid Sequence↗

Studies of the DXS7 polymorphism at the MAO loci in unipolar depression.

From the fact that DXS7 polymorphism is closely related to monoamine oxidase (MAO) genes and MAO inhibitors are widely used in the treatment of unipolar depression, it is of particular interest to study the relationship between the DXS7 polymorphism and unipolar depression. Thus, this study examined the possible association between DXS7 polymorphism and unipolar depression in 66 cases versus 85 controls from Shanghai. Polymerase chain reaction and amplification fragment length polymorphism techniques were used for genotyping of the DXS7 locus in this study. Four alleles at the DXS7 locus were detected with length generated by polymerase chain reaction amplification ranging from 157 to 167 bp. Comparison of allele frequency in the DXS7 locus showed no difference between unipolar depression cases and normal controls in the total population set. When subclassified by age, a significant difference of allele frequency distribution was observed between early onset (before age 40) and late onset (after age 40) patients. The frequency of the 157-bp allele was decreased, whereas the frequency of the 165 allele was increased in late onset patients (0.3810 for the 157-bp allele and 0.5238 for the 165-bp allele) compared with that of early onset patients (0.6304 for the 157-bp allele and 0. 3261 for the 165-bp allele). There was also a difference of allele frequency between patients and normal controls with age over 40 years. The frequency of 165-bp allele increased significantly in late onset patients (0.5238) compared with that of controls within the same age range (0.3454). Association studies suggested that in the population with age over 40 years, presence of the 165-bp allele of DXS7 locus was significantly associated with unipolar depression (relative risk = 2.08, P < 0.05), whereas in the total population set, this association did not exist. Am. J. Med. Genet. (Neuropsychiatr. Genet.) 88:598-600, 1999.

Adolescent↗

Efficacy and safety of rizatriptan wafer for the acute treatment of migraine. Rizatriptan Wafer Protocol 049 Study Group.

Rizatriptan is a potent, highly selective 5HT1B/1D agonist with rapid onset of action for acute treatment of migraine. Rizatriptan wafer is a novel, freeze-dried dosage formulation of rizatriptan which rapidly disintegrates on the tongue, is swallowed with saliva, and may be taken without liquids. The efficacy and tolerability of rizatriptan wafer were examined in a placebo-controlled, double-blind, outpatient study in 555 migraineurs. The primary efficacy endpoint was pain relief at 2 h. From 30 min onwards, significantly more patients experienced pain relief and became pain-free after rizatriptan 10-mg wafer compared to placebo. At 2 h, the percentage of patients with pain relief was significantly higher after rizatriptan 10-mg wafer (74%), 5-mg wafer (59%) compared with placebo (28%). Rizatriptan 10-mg wafer was superior to rizatriptan 5-mg wafer on pain relief at 1.5 and 2 h (p < 0.05). Significantly more patients were pain-free at 2 h after rizatriptan 10-mg wafer (42%), 5-mg wafer (35%) compared with placebo (10%). Both doses of rizatriptan wafer were well tolerated. Rizatriptan wafer is a convenient, highly effective new formulation for acute treatment of migraine.

Administration, Oral↗

Time-to-event analysis, or who gets better sooner? An emerging concept in headache study methodology.

Survival analysis, or, more generally, time-to-event analysis, is of interest when the data represent the time to a defined event. While well established in oncology, it has not been widely applied to migraine research, possibly because the data are usually collected intermittently, rather than continuously, and because of the awkwardness of interpreting treatment effect in survival terms. However, it represents an interesting approach for the analysis of time-to-headache relief, which addresses the clinically relevant question of who gets better sooner. The analysis uses data from all time-points to define the likelihood of headache relief following treatment throughout the entire assessment period. These data can then be used to quantify and test the difference between two therapies.

Clinical Trials as Topic↗

[Genetic association between mood disorder and monoamine oxidase gene].

OBJECTIVE: To ascertain whether the mood disorder (bipolar and unipolar) is genetically associated with genes polymorphisms of MAOA type and MAOB type in the Chinese. METHODS: One hundred and thirty-two cases of Chinese with mood disorder were genotyped for the MAOA(CA)n, MAOB(GT)n and MAOB(TG)n locus using Amp-FLP. RESULTS: Among 132 cases with mood disorder, 8 alleles (size: 112-126 bp) of MAOA(CA)n, 12 alleles (size: 168-198 bp) of MOAB(GT)n and 9 alleles (size: 195-213 bp) of MAOB(TG)n locus were observed. Comparison of the polymorphisms of all alleles in the three locus showed that no significant difference (P > 0.05) was seen in the frequency distribution between cases with mood disorder (bipolar and unipolar) and controls, but the frequency of 180 bp allele for MAOB(GT)n and 250 bp allele for MAOB(TG)n was significantly different (P < 0.05) between the two groups. CONCLUSION: MAO gene (type A and B) is not associated with mood disorder in the Chinese.

Adult↗

[HRV analysis system based on Windows 95 and its preliminary application].

Objective. To provide a real useful application system for the HRV research. Method. The acquisition, detection and analysis system of HRV signal was set up based on Windows 95. The system analyzes the HRV signal with statistic method in time domain and power spectrum in frequency domain. And the power spectrum array was also introduced into the analysis. HRV signals of some healthy persons and some patients were detected and analyzed. Result. The HRV characteristic is much more obvious in the diabetics patients. Conclusion. The system is useful in HRV signal analysis and cardiovascular research.

Aerospace Medicine↗

Transcriptional control of the galanin gene. Tissue-specific expression and induction by NGF, protein kinase C, and estrogen.

Galanin is a neuropeptide widely expressed in the central and peripheral nervous system where it acts as a neurotransmitter/neuromodulator and possibly an immunoregulator and growth factor. Galanin gene expression is highly regulated during development and by certain hormones and injury situations. We have examined transcriptional control mechanisms for this gene using chimeric bovine galanin/luciferase reporter genes. These were analyzed in cultured cells and in transgenic mice. The studies reveal that enhancer and silencer sequences are involved in conferring cell- and tissue-specific expression, and that specific elements close to the promoter are responsible for nerve growth factor and protein kinase C induction. So far, the studies have not revealed sequences on the bovine gene that mediate the action of estrogen.

Animals↗

Characterization of phorbolester-inducible human neuronal factors involved in trans-activation of the galanin gene.

The expression of the neuropeptide galanin (GAL) is elevated in vivo upon nerve stimulation, injury, and in vitro by phorbol 12-myristate-13-acetate (PMA), suggesting that a signal pathway involving protein kinase C activation may be involved in GAL-gene activation. When plasmids containing a different length of the bovine GAL-promoter fused to luciferase were transfected into the human neuroblastoma cell line (SK-N-SH subclone SH-SY5Y), a PMA-responsive element was identified in the promoter-region -68 to -46 base pairs (bp). Co-transfection experiments with plasmids expressing cJun and cFos revealed that they could act alone, as well as synergistically with PMA to induce luciferase activity. Electrical mobility shift assays revealed that a cAMP response element (CRE)-like sequence (TGACGCGG; -59 to -52 bp) bound PMA-inducible nuclear proteins present in SH-SY5Y cells. These proteins appear to bind mainly as CRE-binding protein/activating-transcription-factor (CREB/ATF) and Jun/ATF heterodimers. In addition, an apparent PMA-inducible protein(s) not recognized by CREB/ATF and Jun antibodies bound to the CRE-like containing probe.

Activating Transcription Factor 2↗

Rizatriptan (MAXALT) for the acute treatment of migraine and migraine recurrence. A placebo-controlled, outpatient study. Rizatriptan 022 Study Group.

Rizatriptan is a novel 5-HT1B/1D agonist which is rapidly absorbed after oral administration. The efficacy and tolerability of oral rizatriptan (5 mg and 10 mg) were examined in this multicenter, double-blind, outpatient study of 1473 migraineurs which featured randomized, placebo-controlled treatment of migraine recurrences. On experiencing moderate or severe migraine headaches, patients rated headache severity prior to dosing and at 30-minute intervals for 2 hours after dosing. Onset of effect was seen as early as 30 minutes after dosing with rizatriptan 10 mg. At 2 hours postdose, the percentage of patients with pain relief was significantly higher after rizatriptan 5 mg (62%) or 10 mg (71%) compared with placebo (35%). Complete relief was also significantly higher after rizatriptan 5 mg (33%) and 10 mg (42%) compared with placebo (10%). In patients experiencing headache recurrence after initial benefit, further relief was obtained in 71% with rizatriptan 5 mg (placebo 54%) and in 82% with rizatriptan 10 mg (placebo 44%). Complete relief of recurrent headache was obtained in 36% with rizatriptan 5 mg, 49% with rizatriptan 10 mg, and 15% with placebo (P < 0.05). The most common drug-related adverse experiences were dizziness, somnolence, asthenia/fatigue, and nausea (the incidences of which were low and dose related). There was no increase in the incidence of adverse experiences after use of up to three doses of rizatriptan within 24 hours. We conclude that both doses of rizatriptan are effective and well tolerated in the acute treatment of migraine and migraine recurrence, with the 10-mg dose preferred as it is more effective with a faster onset of action.

Acute Disease↗

[Effect of cyclic loads on revascularization in healing of bone defect].

In order to study the biomechanical effect of cyclic loads on revascularization in bone healing, 20 rabbits were chosen for following experiments. Two 2 mm in diameter holes were made at the middle segment of both right and left tibia. A 2 mm in diameter nail was put in 15 mm proximal to the upper hole, and another was put in 15 mm distal to the lower hole. The wound was covered by direct suture with the ends of the nails kept 15 mm out of skin. The medial ends of the two nails were fixed by an iron plate, while the lateral ends were left for cyclic loads. Three Hz cyclic loads, which was near to the cyclic forces when a rabbit runs, was added to the left tibia for experiment, and no loads was add to the right tibia for control. A group of five rabbits were sacrificed respectively in 5, 10, 20 and 30 days postoperatively. The solution of 2% India ink and gelatin was irrigated from aorta to the bone defects. Then the tibia was removed for histologic study. The changes of cells and microvessel were observed. It was shown that the revascularization in experiment group was about 7 days earlier than that of control. The effect was at its peak from 10 to 30 days. It was concluded that cyclic loads could promote revascularization in the healing process of bone defect.

Animals↗

[A multiexponential model in cavity ring-down absorption spectroscopy].

A multiexponential model of cavity ring-down absorption spectroscopy is established for taking into account the laser linewidth effects. It is demonstrated that by fitting the logarithmic ring-down function to a truncated polynomial, absorption coefficent can be extracted from coefficients of the first as well as higher order terms of the fitted polynomial. The new fit model results in higher accuracy and broader dynamic range than the previous single exponential model.

English Abstract↗

Fibronectin type III repeats mediate RGD-independent adhesion and signaling through activated beta1 integrins.

Many cell-surface and extracellular matrix proteins contain multiple modular domains known as fibronectin type III (FNIII) repeats. Cells adhere to the extracellular matrix proteins fibronectin and tenascin in part by the interaction of certain integrins with the Arg-Gly-Asp (RGD) sequence, displayed on specific FNIII repeats. We have found that, after experimental activation of beta1 integrins, a number of cell types adhere and spread on FNIII repeats lacking RGD, derived from extracellular matrix proteins and cytokine receptors. Interaction between individual FNIII domains and beta1 integrins mediates focal adhesion kinase phosphorylation and subsequent stress fiber and focal contact formation. These data suggest that many FNIII-containing proteins may bind and signal through activated beta1 integrins, dramatically expanding the potential for integrin-dependent intercellular and cell-matrix communication.

Animals↗

[Preparation and clinical application of blocking glue for cancerous serosa].

The blocking glue of cancerous serosa (F-TH glue) is unharmful to human body. It has characteristics of shorter solidification time to become membrane, good elasticity and close adherence to tissue, mainly used for covering cancerous serosa in operation to prevent dropping of cancer cells. In this group, F-TH glue was used in 200 cases of gastrointestinal cancer, in which 75 had positive results of imprinting slice of cancerous serosa, and all became negative. It was confirmed that the glue adhered to cancerous serosa firmly and formed intact protective membrane. No rhagades and dropping of glue were seem by naked eye magnifying glass and electron microscope. The membrane of glue forbid cancer cells not penetrated. It was an excellent glue to block the cancerous serosa.

Cyanoacrylates↗

[Preliminary studies on proliferation of hemorrhagic fever with renal syndrome virus in Leptotrombidium (L.) Scutellare].

In order to observe further the proliferation and kinetic changes of hemorrhagic fever with renal syndrome virus (HFRSV) in Leptotrombidium (L.) Scutellare infected with HFRSV, the raised Leptotrombidium (L.) Scutellare which were at larve stage or at nymph stage were grinded and sterilized by filtration at interval of 20 days, each batch of the filtrate was inoculated separately to Vero-E6 cells and the titre (TCID50/ml) of HFRSV was measured. The results confirmed: HFRSV were isolated from each batch of larve besides the batch at the 60th days, and the titre of HFRSV was -10(-1)-10(-4); HFRSV were also isolated from two batches of nymph. The isolated HFRSV were amplified by PCR technique and the HFRSV RNA were positive. The above results give rise to evidence that Leptotrombidium (L.) Scutellare might be the transmission vector of HFRSV.

Animals↗

Effect of hypoxia and reoxygenation on regional activity of nitric oxide synthase in brain of newborn piglets.

The activity of nitric oxide synthase (NOS) was measured in homogenates from cortex, striatum, hippocampus, cerebellum, pons, thalamus and midbrain of the brain of newborn piglets and the effects of hypoxia and posthypoxic period on this activity was evaluated. The control activities were 19.7, 31.5, 26.8, 16.7, 33.6, 19.3 and 39.4 pmol/mg protein per min, respectively. A 1 h period of hypoxia (an FiO2 of 7%) resulted in statistically significant decreases in the activity of NOS in every region of the brain except for the cortex, where the activity was not significantly altered compared to control. By 2 h of reoxygenation following such a hypoxic episode, the NOS activities increased to above control levels in all regions of the brain, but this increase was statistically significant compared to control only in thalamus. Since hypoxia induced the greatest decrease in NOS activity in the cerebellum, the kinetic constants of the enzyme were measured in homogenates from this region of brain. The decreased activity following the hypoxic episode was associated with an approximately four-fold increase in the apparent affinity (KM) for arginine with no significant change in the maximal rate of reaction (Vmax). The decrease in NOS activity subsequent to a hypoxic episode may contribute to the disturbances in cellular metabolism in the immature brain induced by episodes of hypoxia-reoxygenation.

Animals↗

Rizatriptan vs sumatriptan in the acute treatment of migraine. A placebo-controlled, dose-ranging study. Dutch/US Rizatriptan Study Group.

BACKGROUND: Rizatriptan (MK-462) is a new 5-hydroxytryptamine1D (serotonin1D; 5-HT1D) receptor agonist for the acute treatment of migraine that has improved pharmacokinetic properties compared with sumatriptan succinate. OBJECTIVE: To assess the efficacy and tolerability of 10-, 20-, and 40-mg doses of oral rizatriptan vs a 100-mg dose of oral sumatriptan succinate and placebo for the acute treatment of migraine. DESIGN: Randomized, double-blind, parallel-group, placebo-controlled, outpatient trial. SETTING: Ten US and 4 Dutch investigator centers. PATIENTS: Patients who had migraine with or without aura (N = 449). MAIN OUTCOME MEASURE: The proportion of patients whose conditions improved from severe or moderate headache immediately before dosing to mild or no headache at 2 hours after drug administration (ie, headache relief). RESULTS: The proportion of patients with headache relief was 18% for placebo; 46% for sumatriptan; and 52% for 10-mg, 56% for 20-mg, and 67% for 40-mg rizatriptan. All differences with placebo were statistically significant (P < .001), and 40-mg rizatriptan was superior to sumatriptan (P = .01). The proportion of patients who became free of pain at 2 hours was 3% for the placebo-treated group; 22% for the sumatriptan-treated group; and 26%, 35%, and 47% for the group of patients who took the 10-, 20-, and 40-mg doses of rizatriptan, respectively (all differences with placebo, P < .005; 40-mg rizatripan vs sumatriptan, P = .001). The recurrence of headache within 24 hours was found to be equal across all treatment groups-approximately 40%. Adverse events (most commonly short-lasting mild or moderate dizziness and drowsiness) occurred more frequently after a 40-mg dose of rizatriptan was given than after the other treatments. CONCLUSIONS: The antimigraine effect of 10- and 20-mg rizatriptan was superior to placebo, and comparable with that of 100-mg sumatriptan succinate; the efficacy of 40-mg rizatriptan was superior to that of both placebo and 100-mg sumatriptan succinate, although it was associated with a high frequency of adverse events.

Adult↗

Microsurgical replantation of the avulsed scalp: report of 20 cases.

Our 4-year experience with 20 patients who had suffered avulsion of 75 percent or more of the scalp is reviewed. All patients underwent replantation using microsurgical technique with 100 percent survival in 16, partial survival in 3, and failure in only 1 case. The emergency management and indications for replantation are demonstrated. The roles of sufficient preoperative preparation, generous debridement of damaged vessels, interpositional vein grafts, and the shortening of operative time in contributing to this success are emphasized. We developed a new surgical procedure called simultaneous vein grafts on donor and recipient sites in an effort to use less time in the anastomosis of interpositional vein grafts. Furthermore, we anastomosed the extra artery of the scalp to the vein on the recipient head when no suitable vein could be found. Intraoperative repair of the scalp sensory nerve and no postoperative use of any vasodilator or anticoagulant are discussed.

Adolescent↗