Biomedical subjects

Y Yu

Publications and source records attributed to Y Yu.

At least 253 records · Page 14Linked to original sources

PubMed1999

Improving high-resolution MR bold venographic imaging using a T1 reducing contrast agent.

Recently, a new imaging method was proposed by Reichenbach et al (Radiology 1997;204:272-277) to image small cerebral venous vessels specifically. This method, referred to as high-resolution blood oxygen level-dependent venography (HRBV), relies on the susceptibility difference between the veins and the brain parenchyma. The resulting phase difference between the vessels and the brain parenchyma leads to signal losses over and above the usual T2* effect. At 1.5 T, a rather long TE (roughly 40 msec) is required for this cancellation to become significant, leading to enhanced susceptibility artifacts and a long data acquisition time. In this study, we examine the utility of incorporating a clinically available T1 reducing contrast agent, Omniscan (Sanofi Winthrop Pharmaceuticals, NY, NY), with the HRBV imaging approach to reduce susceptibility artifacts and imaging time while maintaining the visibility of cerebral veins. Using a double-dose injection of Omniscan, we were able to reduce TE from 40 to 25 msec. This led to a decrease in TR from 57 to 42 msec, allowing a 26% reduction in data acquisition time while maintaining the visibility of cerebral venous vessels and reducing susceptibility artifacts. J. Magn. Reson. Imaging 1999;10:118-123, 1999.

Artifacts↗

PubMed1999

Combination of multiple serum markers using an artificial neural network to improve specificity in discriminating malignant from benign pelvic masses.

A panel of four selected tumor markers, CA 125 II, CA 72-4, CA 15-3, and lipid-associated sialic acid, was analyzed collectively using an artificial neural network (ANN) approach to differentiate malignant from benign pelvic masses. A dataset of 429 patients, 192 of whom had malignant histology, was retrospectively used in the study. A prototype ANN classifier was developed using a subset of the data which included 73 patients with malignant conditions and 101 patients with benign conditions. The ANN classifier demonstrated a much improved specificity over that of the assay CA 125 II alone (87.5% vs 68.4%) while maintaining a statistically comparable sensitivity (79.0% vs 82.4%) in discriminating malignant from benign pelvic masses in an independent validation test using data from the remaining 255 patients which had been set aside and kept blind to the developers of the ANN system. A similar improvement in specificity was observed among patients under 50 years of age (82.3% vs 62.0%). The ANN system was further tested using additional serum specimens collected from 196 apparently healthy women. The ANN system had a specificity of 100.0% compared to that of 94.8% with the assay CA 125 II alone.

Antigens, Tumor-Associated, Carbohydrate↗

PubMed1999

13C NMR of liquid crystals with different proton homonuclear dipolar decoupling methods

The effect of several new homonuclear dipolar decoupling methods (frequency-switching Lee-Goldburg decoupling and two sequences based on z-rotational decoupling) on the 13C spectra of liquid crystals has been studied, and the results are compared with those obtained by using two well-established methods (MREV-8 and BLEW-48). For benzene dissolved in two liquid crystalline solvents, BLEW-48 gives the best spectral resolution. The BLEW-48 sequence has also been applied to the 2D method of proton-encoded local field (PELF) spectroscopy to study a bulk liquid crystal, 4-n-pentyl-4'-cyanobiphenyl (5CB). The results are compared with those obtained by using MREV-8, and it is suggested that the BLEW-48 sequence may be preferable to MREV-8 for application in the PELF method. Copyright 1999 Academic Press.

Journal Article↗

PubMed1999

Multiplex inheritance of component phenotypes in a murine model of lupus.

We analyzed the linkage of GN and a wide spectrum of serological phenotypes associated with systemic lupus erythematosus in a (NZM2410 x C57BL/6)F2 cross. Some phenotypes, such as glomerulonephritis (GN) and anti-chromatin IgG antibody production, were more penetrant in females, but others, such as anti-dsDNA antibody production, did not show a gender bias. These results suggest that gender bias affects only a subset of SLE-component phenotypes, and that NZM2410 can be used to dissect the genetic basis of this phenomenon. Genome scanning linked six chromosomal intervals with the expression of one or more component phenotypes. These loci included two Sle loci previously identified in an (NZM2410 x B6)F1 x NZM2410 backcross, loci identified by others in the NZB/W model. Our analysis also suggested two new intervals on chromosomes (Chrs.) 10 and 11. Detailed analysis of the segregation of different phenotypes within these intervals suggests that they encompass more than one susceptibility locus. This clustering has been a common finding in several murine polygenic traits. Each of NZM2410 susceptibility loci can be aligned with a specific genetic pathways contributing to SLE pathogenesis on the basis of the spectrum of component phenotypes expressed.

Animals↗

PubMed1999

Hemorrhage and renal ischemia-reperfusion upregulates the epidermal growth factor receptor in rabbit duodenum.

To study the role of EGF-R in small intestinal adaptation to hemorrhage and I/R, anesthetized rabbits were implanted aseptically with arterial and venous catheters and bilateral renal artery Doppler flow probes and silastic occluders and allowed to recover. Rabbits were then randomly assigned to one of six groups: time control; hemorrhage (22.5 mL/kg) and 2.5 hours of renal occlusion (hemorrhage plus I/R); hemorrhage plus I/R and 2:1 LRS resuscitation; hemorrhage plus I/R and 3:1 LRS resuscitation; hemorrhage alone; or I/R alone. Rabbits were killed 48 hours after hemorrhage, and a section of duodenum was collected for analysis. Hemorrhage plus I/R induced a 2.5-fold increase in EGF-R tyrosine kinase activity compared with that found in the control group (P < .05), and this effect was not modified by either LRS resuscitation regimen. This increased activity was associated with similar Increases in EGF-R protein concentrations and approximately a 50% increase in EGF-R messenger (m)RNA levels compared with levels found in the control group. Further analysis of possible regulatory mechanisms for the increased EGF-R expression after hemorrhage plus I/R detected higher levels of EGF-R phosphorylation compared with those found in the control group but no significant increases in transforming growth factor-alpha mRNA levels. These data, coupled with a significant increase in duodenal thlobarbituric acid-reactive substance concentrations from rabbits in the hemorrhage plus I/R group, support the hypothesis that tyrosine kinase signal transduction pathways involving the EGF-R are activated in the small intestine after hemorrhage, renal I/R, or both, and this process may be mediated, at least in part, by oxidant stress.

Animals↗

PubMed1999

Effect of intravesical nitric oxide therapy on cyclophosphamide-induced cystitis.

PURPOSE: This study was conducted to examine effects of nitric oxide (NO) donors on bladder hyperactivity induced by cyclophosphamide (CYP)-induced cystitis. MATERIALS AND METHODS: Female Sprague-Dawley rats received a single intraperitoneal injection of CYP (100 mg./kg.), and then their micturition pattern including mean micturition volume and the number of micturitions during 24 hours was recorded in a metabolic cage before and after CYP treatment. Forty-eight hours after CYP injection, bladder function under urethane anesthesia was evaluated by cystometry with continuous saline infusion (0.04 ml. per minute) or under isovolumetric conditions (0.8 ml. bladder volume). NO donors, S-nitroso-N-acetyl-penicillamine (SNAP, 2 mM) or sodium nitroprusside (SNP, 1 mM), and an NO synthase (NOS) inhibitor, N-nitro-L-arginine methyl ester (L-NAME, 20 mM) were administered intravesically. Direct action of SNAP on bladder afferent neurons was also tested in a patch-clamp recording study. RESULTS: The number of micturitions significantly increased during the first 24 hours after CYP injection (19.0 +/- 0.88 versus 92.1 +/- 16.3 micturitions/24 hours, mean +/- SE, n = 25) (p <0.001). There was no significant difference in total micturition volume before (12.3 +/- 1.0 ml./24 hours) and after CYP treatment (15.6 +/- 1.5 ml./24 hours). During continuous infusion cystometry, intercontraction interval (ICI) was smaller in CYP-injected rats than in control rats. In CYP-injected animals, NO donors increased the ICI, but did not change the amplitude of bladder contractions. Continuous intravesical infusion of the NOS inhibitor did not alter the cystometric parameters. During cystometry under isovolumetric conditions, contraction frequency was decreased after NO donor administration. NO donors did not influence bladder activity in control rats. In patch clamp recordings, when SNAP (500 microM) was directly applied to dissociated afferent neurons innervating the urinary bladder, high-voltage-activated Ca2+ channel currents were suppressed by approximately 30%. CONCLUSIONS: Intravesical NO donors can suppress CYP-induced bladder hyperactivity. We hypothesize that the effect of NO donors is not due to smooth muscle relaxation, but rather due to an inhibitory effect on bladder afferent pathways that was manifested by an increase in intercontraction interval without changes in contraction amplitude. NO donors may be considered as a possible treatment of CYP-induced and other types of bladder inflammation.

Administration, Intravesical↗

PubMed1999

High signal-to-noise FLASH imaging at 8 Tesla.

A radio frequency (RF) and gradient spoiled fast low angle shot technique was used to acquire images from the human brain at 8 Tesla. The resulting FLASH images, obtained with a 17 degrees nutation, a 70 ms repetition time, and a 17 ms echo time, displayed an average signal-to-noise ratio (SNR) of 220:1 (slice thickness 2.2 mm, field-of-view 24 cm, matrix 256 x 128). These images were compared with images obtained at 1.5 Tesla using identical parameters yielding a signal-to-noise of less than 10:1. As such, the 8 Tesla images display a remarkable improvement in SNR with increasing field strength. The images also show little evidence of susceptibility distortion, chemical shift, or RF penetration limitations.

Brain↗

PubMed1999

A double interaction screen identifies positive and negative ftz gene regulators and ftz-interacting proteins.

Regulatory genes directing embryonic development are expressed in complex patterns. The Drosophila homeobox gene fushi tarazu (ftz) is expressed in a striped pattern that is controlled by several discrete and large cis- regulatory elements. One key cis-element is the ftz proximal enhancer which is required for stripe establishment and which mediates autoregulation by direct binding of Ftz protein. To identify the trans-acting factors that regulate ftz expression and autoregulation, we developed a modified yeast two hybrid screen, the Double Interaction Screen (DIS). The DIS was designed to isolate both DNA binding transcriptional regulators that interact with the proximal enhancer and proteins that interact with Ftz itself when it is bound to the enhancer. The screen identified two candidate Ftz protein cofactors as well as activators and repressors of ftz transcription that bind directly to the enhancer. One of these (Tramtrack (Ttk)) was previously shown to bind to at least five sites in the proximal enhancer; genetic studies suggested that Ttk acts as a repressor of ftz in the embryo. Here we show that, in yeast cells, Ttk protein strongly activates transcription, suggesting that yeast may be missing a necessary co-repressor which is present in Drosophila embryos. Further, we have characterized the activity of a second candidate ftz repressor isolated in the screen - the product of the pair-rule gene sloppy paired - a member of the forkhead family. We show that Slp1 is a DNA binding protein. We have identified a high affinity binding site for Slp1 in the ftz proximal enhancer. Slp1 represses transcription via this binding site in yeast cells, consistent with its role as a direct repressor of ftz stripes in interstripe regions during late stages of embryogenesis. The DIS should be a generally useful method to identify DNA binding transcriptional regulators and protein partners of previously characterized DNA binding proteins.

Animals↗

PubMed1999

Radioiodinated antibody targeting of the HER-2/neu oncoprotein: effects of labeling method on cellular processing and tissue distribution.

Monoclonal antibody (MAb) internalization can have a major effect on tumor retention of radiolabel. Two anti-HER-2/neu MAbs (TA1 and 520C9) were radioiodinated using the iodogen, N-succinimidyl 5-iodo-3-pyridinecarboxylate (SIPC), and tyramine-cellobiose (TCB) methods. Paired-label studies compared internalization and cellular processing of the labeled MAbs by SKOv3 9002-18 ovarian cancer cells in vitro. Intracellular radioiodine activity for 520C9 was up to 2.6 and 3.0 times higher for SIPC and TCB labeling, respectively, compared with iodogen. Likewise, intracellular activity for TA1 was up to 2.3 and 2.9 times higher with the SIPC and TCB methods compared with iodogen labeling. Unfortunately, similar advantages in tumor accumulation were not achieved in athymic mice bearing SKOv3 9008-18 ovarian cancer xenografts.

Animals↗

PubMed1999

Application of amino acid type-specific 1H- and 14N-labeling in a 2H-, 15N-labeled background to a 47 kDa homodimer: potential for NMR structure determination of large proteins.

NMR investigations of larger macromolecules (> 20 kDa) are severely hindered by rapid 1H and 13C transverse relaxation. Replacement of non-exchangeable protons with deuterium removes many efficient 1H-1H and 1H-13C relaxation pathways. The main disadvantage of deuteration is that many of the protons which would normally be the source of NOE-based distance restraints are removed. We report the development of a novel labeling strategy which is based on specific protonation and 14N-labeling of the residues phenylalanine, tyrosine, threonine, isoleucine and valine in a fully deuterated, 15N-labeled background. This allows the application of heteronuclear half-filters, 15N-editing and 1H-TOCSY experiments to select for particular magnetization transfer pathways. Results from investigations of a 47 kDa dimeric protein labeled in this way demonstrated that the method provides useful information for the structure determination of large proteins.

Amino Acid Sequence↗

PubMed1999

Genetic diversity of cattle in south China as revealed by blood protein electrophoresis.

Genetic variation of 31 blood protein loci in 236 cattle from eight South China populations (including mithan, Bos frontalis) and a Holstein population was investigated by means of horizontal starch gel electrophoresis. Thirteen loci (ALB, CAR, Hb-b, Np, PGM, Amy-I, PEP-B, AKP, 6PGD, Cp, Pa, EsD, and TF) were found to be polymorphic. The comparison of average heterozygosities (H) shows that all the native cattle embrace a rich genetic diversity. Our results on protein polymorphism suggest that cattle in China originated mainly from Bos indicus and Bos taurus; Xuwen, Hainan, Wenshan, and Dehong cattle and the Dehong zebu are close to zebu-type cattle, and Diqing and Zhaotong cattle are close to the taurine. The mithan was very different from other native cattle, and we suggest that its origin was complicated and may be influenced by other cattle species.

Alleles↗

PubMed1999

Mitochondrial DNA variation in cattle of south China: origin and introgression.

Ten restriction endonucleases were used to investigate the mitochondrial DNA restriction fragment length polymorphism (mtDNA RFLP) of 11 native cattle breeds and one cultivated cattle breed in South China. Twenty-three restriction morphs were detected, which can be sorted into five haplotypes. A phylogenetic tree of the haplotypes was constructed by using the 'upgMa' method. Our study showed that haplotype I and II are identical to the zebu (Bos indicus) and taurine (Bos taurus) haplotypes, respectively. Zebu and taurine were the two major origins of cattle populations in South China, and the zebu probably had more influence on the native cattle population than taurine did. Haplotype III is identical to haplotype I of yak (Bos grunniens), which was only detected in the Diqing cattle breed. Haplotype IV was detected for the first time. This haplotype, found only in Dehong cattle, might be from an independent domestication event, probably from another Bos indicus population. Divergence of haplotypes I and IV occurred about 268,000-535,000 years ago, much earlier than the 10,000-year history of cattle husbandry. Our results also suggest a secondary introgession of mtDNA from yak to Diqing cattle.

Animal Husbandry↗

PubMed1999

NMR studies on the 46-kDa dimeric protein, 3,4-dihydroxy-2-butanone 4-phosphate synthase, using 2H, 13C, and 15N-labelling.

3,4-Dihydroxy-2-butanone 4-phosphate synthase catalyses the release of C-4 from the substrate, ribulose phosphate, via a complex series of rearrangement reactions. The cognate ribB gene of Escherichia coli was hyperexpressed in a recombinant E. coli strain. The protein was shown to be a 46-kDa homodimer by hydrodynamic analysis. A variety of protein samples labelled with different grades of 13C, 15N and 2H, i.e. one with 100% 2H and 15N, one with 75% 2H, 99% 13C, 15N, and one with 100% 2H, 99% 13C,15N were prepared. Despite the large molecular size, 2- and 3-dimensional NMR spectra of reasonable quality were obtained. Attempts at the assignment of individual 13C, 15N and 1H signals show, in principle, the feasibility of structure determination. The number of NMR signals shows unequivocally that the homodimeric protein obeys strict C2 symmetry.

Base Sequence↗

PubMed1999

Expression of growth factors in the mandibular distraction zone: a sheep study.

Interest in craniofacial osteodistraction has increased in recent years parallel with the growing attention given to the role of growth factors in tissue healing and regeneration. This study was embarked upon to investigate the expression of bFGF, TGF-beta and IGF-1 in the distraction zone of the mandible. Fourteen growing sheep were allocated to three experimental groups. Six animals were allocated to Groups A and B (n = 12) and underwent bilateral mandibular corticotomies with fixation of an external lengthening device. The distraction protocol consisted of a rate of 1.0 mm/day (twice daily) for 20 days followed by a consolidation phase of 20 days after which the sheep were sacrificed. Group C comprised of age matched sham operated animals (n = 2). Bone histochemistry for growth factors were performed in the harvested mandibles. A strong staining of bFGF was seen in the osteoblasts, osteocytes and osteoid matrix following 20 days of distraction and 20 days of consolidation compared to the control group. TGF-beta and IGF-1 demonstrated mild but clear staining in osteocyte and osteoblast cells and TGF-beta stained positively in the osteoid seam in the experimental groups. These finding suggest that bFGF, IGF-1 and TGF-beta may play different roles in the remodelling phase of distraction osteogenesis.

Animals↗

PubMed1999

The role of transforming growth factor-beta, insulin-like growth factor I, and basic fibroblast growth factor in distraction osteogenesis of the mandible.

Distraction osteogenesis is a viable method for regenerating large amounts of bone. In contrast to fracture healing, the mode of bone formation in distraction osteogenesis is primarily intramembranous ossification. The basic biology of the process is still not well understood. The growth factor cascade is likely to play an important role in distraction. This study examines the growth factor cascade in a lengthened ovine mandible model. Twenty-four animals were divided into four groups with varying rates of distraction (1, 2, 3, and 4 mm/day). A unilateral distractor at the angle of the mandible was used. The mandibles were lengthened to 24 mm and fixed for a period of 5 weeks, after which the animals were killed. The sections were probed for transforming growth factor-beta, basic fibroblast growth factor, and insulin-like growth factor I. The growth factors studied were present in all four groups. Transforming growth factor-beta, basic fibroblast growth factor, and insulin-like growth factor I were present in both the bony matrix of the sections and the cytoplasm of the cells, osteoblasts, and a small number of mesenchymal cells. The sections obtained from groups distracted at faster rates showed stronger presence of the growth factors examined by more intense staining. In fracture healing, the localization of transforming growth factor-beta in stage I of healing corresponded with the precise region of intramembranous ossification in stage II. Diffuse presence of transforming growth factor-beta throughout the lengthened region corresponded with the process of intramembranous ossification observed in distraction. In fracture healing, insulin-like growth factor I and basic fibroblast growth factor have been shown to promote proliferation and differentiation of osteoblasts from precursor cells. The intense presence of insulin-like growth factor I and basic fibroblast growth factor in the distracted region may account for osteoblast proliferation and formation from precursor mesenchymal cells. Mechanical strain has been shown to increase the expression of transforming growth factor-beta and insulin-like growth factor I. Distraction may serve as a source of mechanical strain, which may explain, in part, the expression of these growth factors, particularly in the faster groups.

Animals↗

PubMed1999

Induction of human herpesvirus-8 DNA replication and transcription by butyrate and TPA in BCBL-1 cells.

Human herpesvirus-8 (HHV-8) is a gammaherpesvirus that is present primarily in a state of low level persistence in primary effusion lymphoma cell lines. Using BCBL-1 cells that harbour HHV-8 but lack Epstein-Barr virus, we demonstrate that sodium butyrate is much more effective than the phorbol ester 12-O-tetradecanoyl phorbol-13-acetate (TPA) at inducing high levels of class II and III virus transcription and viral DNA replication, but also initiates apoptosis. Apoptosis occurs prior to assembly of virions when high concentrations of butyrate (1-3 mM) are used, whereas reduction of butyrate concentration to 0.3 mM decreases the rate of apoptosis and results in production and secretion of enveloped virions that are visualized at high number by electron microscopy in approximately 20% of BCBL-1 cells. Butyrate induces much higher levels of multiple class II and class III transcripts than does TPA, including v-MIPI, v-IL-6, v-Bcl-2, vGPCR and ORF26. A decrease in concentration of butyrate from 3 to 0.3 mM delays the peak induction of these genes, but peak levels remain higher than peak levels in response to TPA. These studies indicate that the massive apoptosis induced by 3 mM butyrate could be diminished and delayed by reduction of butyrate concentration to 0.3 mM, thereby allowing expression of high levels of lytic-associated genes and production of high yields of HHV-8 virions.

Butyrates↗

PubMed1999

Permanent prostate seed implant brachytherapy: report of the American Association of Physicists in Medicine Task Group No. 64.

There is now considerable evidence to suggest that technical innovations, 3D image-based planning, template guidance, computerized dosimetry analysis and improved quality assurance practice have converged in synergy in modern prostate brachytherapy, which promise to lead to increased tumor control and decreased toxicity. A substantial part of the medical physicist's contribution to this multi-disciplinary modality has a direct impact on the factors that may singly or jointly determine the treatment outcome. It is therefore of paramount importance for the medical physics community to establish a uniform standard of practice for prostate brachytherapy physics, so that the therapeutic potential of the modality can be maximally and consistently realized in the wider healthcare community. A recent survey in the U.S. for prostate brachytherapy revealed alarming variance in the pattern of practice in physics and dosimetry, particularly in regard to dose calculation, seed assay and time/method of postimplant imaging. Because of the large number of start-up programs at this time, it is essential that the roles and responsibilities of the medical physicist be clearly defined, consistent with the pivotal nature of the clinical physics component in assuring the ultimate success of prostate brachytherapy. It was against this background that the Radiation Therapy Committee of the American Association of Physicists in Medicine formed Task Group No. 64, which was charged (1) to review the current techniques in prostate seed implant brachytherapy, (2) to summarize the present knowledge in treatment planning, dose specification and reporting, (3) to recommend practical guidelines for the clinical medical physicist, and (4) to identify issues for future investigation.

Brachytherapy↗

PubMed1999

Proteinmorphosis: a mechanical model for protein conformational changes.

Proteinmorphosis is a physically-based interactive modeling system for simulating large or small conformational changes of proteins and protein complexes. It takes advantage of the cross-linked one-dimensional nature of protein chains. The user can, based on her chemical knowledge, pull pairs of points (lying either on a single protein or on different molecules) together by specifying geometric distance constraints. The resulting conformation(s) of the molecule(s) of interest is computed by an efficient finite element formalism taking into account elasticity of the protein backbone, van der Waals repulsions, hydrogen bonds, salt bridges and the imposed distance constraints. The conformational change is computed incrementally and the result can be visualized as an animation; complete interactivity is provided to position and view the proteins as desired by the user. Physical properties of regions on the protein can also be chosen interactively. The conformational change of calmodulin upon peptide binding is examined as a first experiment. It is found that the result is satisfactory in reproducing the conformational change that follows on peptide binding. We use Proteinmorphosis to study the cooperative hemoglobin oxygen binding mechanism in a second, more sophisticated, experiment. Different modeling strategies are designed to understand the allosteric (cooperative) binding process in this system and the results are found to be consistent with existing hypotheses.

Calmodulin↗