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Biomedical subjects

J Yu

Publications and source records attributed to J Yu.

At least 55 records · Page 3Linked to original sources
PubMed2000

Specific requirement for the p85-p110alpha phosphatidylinositol 3-kinase during epidermal growth factor-stimulated actin nucleation in breast cancer cells.

We have studied the role of phosphatidylinositol 3-kinases (PI 3-kinases) in the regulation of the actin cytoskeleton in MTLn3 rat adenocarcinoma cells. Stimulation of MTLn3 cells with epidermal growth factor (EGF) induced a rapid increase in actin polymerization, with production of lamellipodia within 3 min. EGF-stimulated lamellipodia were blocked by 100 nM wortmannin, suggesting the involvement of a class Ia PI 3-kinase. MTLn3 cells contain equal amounts of p110alpha and p110beta, and do not contain p110delta. Injection of specific inhibitory antibodies to p110alpha induced cell rounding and blocked EGF-stimulated lamellipod extension, whereas control or anti-p110beta antibodies had no effect. In contrast, both antibodies inhibited EGF-stimulated DNA synthesis. An in situ assay for actin nucleation showed that EGF-stimulated formation of new barbed ends was blocked by injection of anti-p110alpha antibodies. In summary, the p110alpha isoform of PI 3-kinase is specifically required for EGF-stimulated actin nucleation during lamellipod extension in breast cancer cells.

Actins↗
PubMed2000

Knock down of spinal NMDA receptors reduces NMDA and formalin evoked behaviors in rat.

Chronic pain remains a major health problem afflicting an estimated 70% of patients with advanced cancer and inflammatory disorders, and up to 94% of patients with spinal cord injuries. Although progress has been made in the pharmacotherapy of chronic pain management, such as usage of adjuvant drugs and more effective methods of drug delivery, the mainstay of clinical pain management still depends on opiates. NMDA receptor activation, at the level of the spinal cord has been shown to play an important role in the facilitation of nociception (pain) in several animal models. Unfortunately, potent NMDA receptor antagonists, such as MK-801 and APV, have toxic properties and low safety margins that preclude their clinical use. We present evidence which indicates that the use of antisense oligonucleotides targeted to the NMDA-R1 receptor subunit (AS-NMDA-R1), but not sense, abolishes NMDA and formalin induced behaviors. Moreover, we demonstrate that spinal administration of AS-NMDA-R1 results in the abolition of staining for immunoreactive NMDA-R1 in the spinal cord. These data provide novel evidence supporting the feasibility of the use of gene therapy approaches in the management of neuropathic pain.

Animals↗
PubMed2000

Estimation of surface electromyogram spectral alteration using reduced-order autoregressive model.

A new method is proposed, based on the pole phase angle (PPA) of a second-order autoregressive (AR) model, to track spectral alteration during localised muscle fatigue when analysing surface myo-electric (ME) signals. Both stationary and non-stationary, simulated and real ME signals are used to investigate different methods to track spectral changes. The real ME signals are obtained from three muscles (the right vastus lateralis, rectus femoris and vastus medialis) of six healthy male volunteers, and the simulated signals are generated by passing Gaussian white-noise sequences through digital filters with spectral properties that mimic the real ME signals. The PPA method is compared, not only with spectra-based methods, such as Fourier and AR, but also with zero crossings (ZCs) and the first AR coefficient that have been proposed in the literature as computer efficient methods. By comparing the deviation (dev), in percent, between the linear regression of the theoretical and estimated mean frequencies of the power spectra for simulated stationary (s) and non-stationary (ns) signals, in general, it is found that the PPA method (devs = 4.29; devns = 1.94) gives a superior performance to ZCs (dvs = 8.25) and the first AR coefficient (4.18 < devs < 21.8; 0.98 < devns < 4.36) but performs slightly worse than spectra-based methods (0.33 < devs < 0.79; 0.41 < devns < 1.07). However, the PPA method has the advantage that it estimates spectral alteration without calculating the spectra and therefore allows very efficient computation.

Adult↗
PubMed2000

Genes encoding cytochrome P450 and monooxygenase enzymes define one end of the aflatoxin pathway gene cluster in Aspergillus parasiticus.

The identification of overlapping cosmids resulted in the discovery of the aflatoxin biosynthetic pathway gene cluster in Aspergillus flavus and A. parasiticus. This finding led to the cloning and characterization of one regulatory and 16 structural genes involved in aflatoxin biosynthesis, including the most recent report on the gene, ordA, which has been identified to be involved in the formation of four aflatoxins (B1, B2, G1 and G2). However, these genes do not account for all the identified chemical/biochemical steps in aflatoxin synthesis and efforts are underway to identify the genes controlling the other steps. We are also attempting to define the outer boundaries of the aflatoxin pathway gene cluster in the Aspergillus genome. For this goal, we extended sequencing in both directions from the existing (60 kb) aflatoxin pathway gene cluster, beyond the pksA gene at one end and the omtA gene at the other. Within the 25-kb genomic DNA sequence determined at the omtA end of the cluster, several new gene sequences were identified. The recently reported genes, vbs and ordA, were found within this 25-kb region. Two additional genes were also found in this region, a cytochrome P450 monooxygenase encoding gene, tentatively named cypX, and a monooxygenase encoding gene, tentatively named moxY, and these are also reported in this study. The sequence beyond these genes showed a 5-kb non-coding region of DNA followed by the presence of a cluster of genes probably involved in sugar metabolism. Northern blot analysis and reverse transcriptase-polymerase chain reaction (RT-PCR) studies demonstrated that the genes, cypX and moxY, are expressed concurrently with genes involved in aflatoxin biosynthesis. Therefore, the two putative aflatoxin pathway genes cypX and moxY followed by a 5-kb non-coding region of DNA define one end of the boundary of the aflatoxin pathway gene cluster in A. parasiticus.

Aflatoxins↗
PubMed2000

A replication origin of Bacillus thuringiensis.

A replication origin of Bacillus thuringiensis (Bt) was found in a Bacillus thuringiensis-Escherichia coli shuttle vector of pHT3101. Deletion analysis showed that the replication origin was segregationally stable at suitable temperature for Bt growth. The fragment containing the replication origin was cloned in pUC18 and sequenced. It was 261 base pairs in length, located in the open reading frame 2 (ORF2) of BTSPB sequence. The 261-bp fragment was cloned in pBR322, creating an improved Bt-E. coli shuttle vector pBR261, which contained two resistance genes responsible for ampicillin and tetracycline. Our study showed that the replication origin structure could be recognized by replication protein of host cells.

Bacillus thuringiensis↗
PubMed2000

Coexpression of cyt1Aa of Bacillus thuringiensis subsp. israelensis with Bacillus sphaericus binary toxin gene in acrystalliferous strain of B. thuringiensis.

The cyt1Aa gene of Bacillus thuringiensis subsp. israelensis and binary toxin gene of Bacillus sphaericus C3-41 were introduced into an acrystalliferous strain of B. thuringiensis independently and in combination by using shuttle vector pBU4. SDS-PAGE and Western blot analysis proved that cyt1Aa and binary toxin genes coexpressed during the sporulation of the recombinant. Transformant strain expressing the Cyt1Aa and binary toxin proteins in combination was more toxic to susceptible and resistant Culex pipiens quinquefasciatus than the transformants expressing Cyt1Aa protein or binary toxin proteins independently. It was suggested that large amount of production of Cyt1Aa protein and binary toxin proteins possibly interacted synergistically, thereby increasing its mosquitocidal toxicity significantly.

Animals↗
PubMed2000

Treatment of VX2 liver tumor in rabbits with "wet" electrode mediated radio-frequency ablation.

Radio-frequency ablation (RFA) has been considered as an alternative therapy for liver tumors. A "wet" electrode with interstitial infusion of hypertonic saline was tested for the RFA of liver tumor in rabbits. Seventy-eight liver tumors ( 1.5 to 3.0 cm) were induced in 41 rabbits by VX2 carcinoma implantation. Fifty-one tumors in 27 rabbits were treated with RFA. Under laparotomy, the RF energy was delivered while 5 % saline was infused through the electrode into the tumor at 1 ml/min. Six rabbits with 12 tumors were treated with only intratumoral 5 % saline infusion without RFA. Another 8 rabbits with 15 tumors received sham operation as untreated controls. The efficacy of the therapy was evaluated with survival rate, MRI, microangiography, and histopathology. In the RFA group, 6 rabbits survived longer than 6 months (absolute eradication rate 22.2 %); 12 rabbits were found free of viable tumor at the moment when they were sacrificed (relative eradication rate 44.4 %); 9 rabbits showed local tumor relapse and/or lung metastasis 2-10 weeks after ablation (recurrent rate 33.3 %). In control groups of saline infusion and sham operation, all 14 rabbits died within 3 months (mortality rate 100 %). Three-month survival rates between RFA group and control groups were significantly different (p < 0.05). Findings of MRI, microangiography, and histology supported these outcomes. Radical treatment of liver malignancy in rabbits is possible with the present modified RFA technique. Its clinical usefulness has to be further proven.

Animals↗
PubMed2000

A novel "cooled-wet" electrode for radiofrequency ablation.

In the light of growing demands for improved applicability of radiofrequency ablation (RFA), recently we have developed a novel "cooled-wet" electrode by taking the advantages of both internally cooled and saline-enhanced electrodes. The efficacy of the electrode was evaluated in both ex vivo and in vivo liver RFA under both low and high power output levels. The ablation volume created with the "cooled-wet" electrode appeared to be much larger than that reported up to now with the use of other monopolar electrodes. The mechanisms on how this device optimizes the RF energy delivery are also discussed.

Animals↗
PubMed2000

Human PRRX1 and PRRX2 genes: cloning, expression, genomic localization, and exclusion as disease genes for Nager syndrome.

In this study, we extend our examination of the function of the Prrx1 (a.k.a Mhox, Prx1, K-2, and Pmx1) as well as Prrx2 (a.k.a. S8 and Prx2) genes by characterizing the expression of the human orthologs and their potential for causing specific human malformations. The expression pattern of PRRX2 and its close relative, PRRX1, were analyzed in human tissue by RT-PCR. Although the expression of these human genes is similar to their mouse orthologs, there are notable differences in expression. PRRX2 was detected in the human kidney and lung, whereas in mice and chickens neither of these tissues has been reported to express Prrx2. For PRRX1 the expression pattern was quite similar to other vertebrates, but the ratio of the two isoforms was reversed. To begin the search for the gene-disease connection, both genes were mapped to human chromosomes by FISH. The PRRX1 locus maps to 1q23, whereas the PRRX2 locus maps to 9q34.1. This localization, along with the recently described phenotypes of the gene-targeted Prrx1, Prrx2 and double mutant mice, enabled us to search the human disease databases for similar malformations. This examination suggested that mutations at the PRRX1 and/or PRRX2 loci could result in Nager Acrofacial Dysostosis (NAFD) syndrome. We obtained DNA samples from eight patients with NAFD, as well as two patients with Miller syndrome, and analyzed them for mutations in the PRRX1 and PRRX2 genes. The data excludes mutations in the presumed coding sequences of these genes from causing NAFD.

Abnormalities, Multiple↗
PubMed2000

Multiple origins of Tibetan Y chromosomes.

The genetic origin of Tibetans was investigated using Y chromosome markers. A total of three populations were studied, two from central Tibet speaking central Tibetan and one from Yunnan speaking Kham. Two dominant paternal lineages (>80%) were identified in all three populations with one possibly from central Asia (YAP+) and the other from east Asia (M122C). We conclude that Tibetan Y chromosomes may have been derived from two different gene pools, given the virtual absence of M122C in central Asia and YAP+ in east Asia, with drift an unlikely mechanism accounting for these observations.

Alu Elements↗
PubMed2000

Novel Approaches to Oral Vaccines: Delivery of Antigens by Edible Plants.

Advances in genetic engineering in the past decade have accelerated the expression, in plants, of foreign proteins with industrial and pharmaceutical value. Antigens from infectious bacterial or viral diseases have been introduced into plants through plant virus-mediated infection or Agrobacterium tumefaciens-mediated stable transformation methods. Oral immunization with transgenic plant tissues that contain vaccine antigen proteins stimulates both systemic and mucosal immune responses in animals. Plant-based vaccines can provide significant levels of protection against challenge by viral or bacterial pathogens.

Journal Article↗
PubMed2000

Urinary function and bother after radical prostatectomy or radiation for prostate cancer: a longitudinal, multivariate quality of life analysis from the Cancer of the Prostate Strategic Urologic Research Endeavor.

PURPOSE: We measure the effect of time on urinary function and bother during the first 2 years following treatment for early stage prostate cancer. MATERIALS AND METHODS: We studied urinary function and bother in 564 men recently diagnosed with early stage prostate cancer and treated with radiotherapy or radical prostatectomy with or without nerve sparing. Outcomes were assessed with the UCLA Prostate Cancer Index, which is a validated, health related quality of life instrument that includes these 2 domains. To minimize the influence of other factors we adjusted for age, co-morbidity, general health, pad use, anticholinergics or procedures for urethral stricture. All subjects were drawn from the Cancer of the Prostate Strategic Urologic Research Endeavor (CaPSURE), which is a national longitudinal database. RESULTS: Urinary function improved with time during the first year after surgery but remained fairly constant during year 2. Urinary function remained stable throughout the 2 years after radiation. Urinary bother was worse after radiation throughout the 2 years, although it improved markedly by the end of year 1. Age, ethnicity and co-morbidity did not impact urinary function or bother but being married did have an advantage. CONCLUSIONS: Patients undergoing surgery or radiation showed different longitudinal profiles of urinary function and bother during the first 2 years after treatment.

Aged↗
PubMed2000

Human cord blood conditioned medium enhances leukemia colony formation in vitro.

Childhood T-cell acute lymphoblastic leukemia (T-ALL) is one of the most common childhood cancers. Recently, we observed that pre-conditioning sub-lethally irradiated immunodeficient mice with human cord blood mononuclear cells facilitates in these mice high level engraftment of primary T-ALL cells obtained from patients. Here we report that human cord blood cells secrete a factor(s) which markedly enhances in vitro both colony number and burst size of the T-ALL clonogenic progenitors from patients. The enhancing activity does not correspond to IL-2, IL-15, nor to several other cytokines implicated in T cell proliferation/activation. Thus, it is possible cord blood may secrete an as yet unidentified factor(s) acting on leukemia clonogenic progenitors of T-ALL. Collectively, these studies should prove invaluable in addressing the growth properties of primary T-ALL cells from patients.

Animals↗
PubMed2000

Conservation in decay accelerating factor (DAF) structure among primates.

The decay accelerating factor (DAF, CD55) protects self cells from activation of autologous complement on their surfaces. It functions to disable the C3 convertases, the central amplification enzymes of the cascade. Its active site(s) are contained within four approximately 60 amino acid long units, termed complement control protein repeats (CCPs), which are suspended above the cell surface on a 68 amino acid long serine/threonine (S/T)-rich cushion that derives from three exons. We previously proposed a molecular model of human DAF's four CCPs in which certain amino acids were postulated to be recognition sites for the interaction between DAF and the C3 convertases. In the current study, we characterized DAF in five non-human primates: the great apes, gorilla and common chimpanzee, and the Old World monkeys: hamadryas baboon, Rhesus macaque, and patas monkey. Amino acid homology to human DAF was approximately 98% for the two great apes and 83% for the three Old World monkeys. The above cited putative ligand interactive residues were found to be fully conserved in all of the non-human primates, although there were amino acid changes outside of these areas. In the chimpanzee, alternative splicing of the S/T region was found potentially to be the source of multiple protein isoforms in erythrocytes, whereas in the patas monkey, similar alternative splicing was observed but only one protein band was seen. Interestingly, a Rhesus macaque was found to exhibit a phenomenon paralleling the human Cromer Dr(a-) blood group, in which a 44-base pair deletion in CCP3 leads to a frameshift and early STOP codon.

Alternative Splicing↗
PubMed2000

Process dissociation as source monitoring.

A 2-high-threshold model source-monitoring model (U. J. Bayen, K. Murnane, & E. Erdfelder, 1996) was applied to both source-monitoring and process-dissociation data collected varying source and distracter similarity. The model fit both sets of data using identical parameter values. The values of the detection parameter, D, and the source-discrimination parameter, d, varied in the manner expected. Also, neither the process-dissociation (L. L. Jacoby, 1991) nor the extended process-dissociation model (A. Buchner, E. Erdfelder, & B. Vaterrodt-Plünnecke, 1995) fit either type of data. The memory processes involved in recognition judgments are the same when using the process-dissociation or the source-monitoring procedure. The 4 cognitive processes in both procedures can be interpreted as item detection, source identification, recognition guessing, and source guessing. The potential role of unconscious memory influences via the 2 guessing processes is discussed.

Adolescent↗
PubMed2000

Receptor-dependent cell stress and amyloid accumulation in systemic amyloidosis.

Accumulation of fibrils composed of amyloid A in tissues resulting in displacement of normal structures and cellular dysfunction is the characteristic feature of systemic amyloidoses. Here we show that RAGE, a multiligand immunoglobulin superfamily cell surface molecule, is a receptor for the amyloidogenic form of serum amyloid A. Interactions between RAGE and amyloid A induced cellular perturbation. In a mouse model, amyloid A accumulation, evidence of cell stress and expression of RAGE were closely linked. Antagonizing RAGE suppressed cell stress and amyloid deposition in mouse spleens. These data indicate that RAGE is a potential target for inhibiting accumulation of amyloid A and for limiting cellular dysfunction induced by amyloid A.

Amyloid↗
PubMed2000

Sampling SNPs.

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Alleles↗