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Biomedical subjects

Y Yu

Publications and source records attributed to Y Yu.

At least 199 records · Page 11Linked to original sources

Rice transposable elements: a survey of 73,000 sequence-tagged-connectors.

As part of an international effort to sequence the rice genome, the Clemson University Genomics Institute is developing a sequence-tagged-connector (STC) framework. This framework includes the generation of deep-coverage BAC libraries from O. sativa ssp. japonica c.v. Nipponbare and the sequencing of both ends of the genomic DNA insert of the BAC clones. Here, we report a survey of the transposable elements (TE) in >73,000 STCs. A total of 6848 STCs were found homologous to regions of known TE sequences (E<10(-5)) by FASTX search of STCs against a set of 1358 TE protein sequences obtained from GenBank. Of these TE-containing STCs (TE-STCs), 88% (6027) are related to retroelements and the remaining are transposase homologs. Nearly all DNA transposons known previously in plants were present in the STCs, including maize Ac/Ds, En/Spm, Mutator, and mariner-like elements. In addition, 2746 STCs were found to contain regions homologous to known miniature inverted-repeat transposable elements (MITEs). The distribution of these MITEs in regions near genes was confirmed by EST comparisons to MITE-containing STCs, and our results showed that the association of MITEs with known EST transcripts varies by MITE type. Unlike the biased distribution of retroelements in maize, we found no evidence for the presence of gene islands when we correlated TE-STCs with a physical map of the CUGI BAC library. These analyses of TEs in nearly 50 Mb of rice genomic DNA provide an interesting and informative preview of the rice genome.

Arabidopsis↗

Theoretical model for an MRI radio frequency resonator.

A theoretical model is described for a magnetic resonance imaging (MRI) radio-frequency resonator (an MRI "coil") that is useful at ultrahigh frequencies. The device is a "TEM resonator," which is based on a concept originally proposed by Röschmann (1988). The coil comprises a circular cavity-like structure containing several coaxial transmission lines operating in a transverse electromagnetic (TEM) mode. The model developed herein treats the empty coil and is based on multiconductor transmission line theory. This work generalizes and extends similar analyses of the device by Röschmann (1995) and Chingas and Zhang (1996). The model employs explicit calculation of per-unit-length parameters for TEM lines having arbitrary geometries. Calculations of the resonator's frequency response are found to compare well with measurements. Fields produced by linear (single-point) and quadrature drive are also computed and compared to images of low-permittivity phantoms.

Electromagnetic Fields↗

Interaction with magnesium and ADP stabilizes both components of nitrogenase from Klebsiella pneumoniae against urea denaturation.

The nitrogenase enzyme of Klebsiella pneumoniae consists of two separable proteins, each with multiple subunits and one or more oxygen sensitive metallocenters. The wild-type nitrogenase proteins are stable to electrophoresis in high concentrations of urea under anaerobic conditions. Addition of Mg+2 and ADP greatly increases the stability of the smaller Fe protein (from <4 to >6 M for full unfolding), an effect directly analogous to stabilization in p21ras induced by Mg+2 and GDP. Stabilization by Mg+2 is slight for the holo MoFe protein (from approximately 1.5 to approximately 2.4 M) but more dramatic for the apo protein form of the MoFe protein accumulated by certain Fe protein (nifH gene) mutants. The potent product inhibitor of nitrogenase function, MgADP, increases stability of the MoFe protein more than Mg+2 alone, to approximately 3.6 M, showing that nucleotides interact with the MoFe protein. Mutations of the nifM gene result in slower accumulation of less stable Fe protein, indicating that NifM is involved in correct folding of the Fe protein. Mutationally altered proteins are often difficult to purify for study because of their inherent instability, low expression level, or oxygen lability. Crude extracts of 11 different mutants of Fe protein (nifH gene) were examined by transverse urea gradient gels to rapidly screen for stabilizing interactions in the presence or absence of substrate or inhibitor analogs. Amino acid alterations D44N and R188C, at the interface of the dimer, in the vicinity of the nucleotide binding site(s), have significantly lower stability than the wild-type enzyme in the absence of Mg+2 but comparable stability in its presence, showing the importance of Mg+2 in the subunit interactions. Mutations N163S and E266K, in which residues normally involved in hydrogen bonding far from the active site were altered, are more labile than the wild-type even with Mg+2 added. Seven other mutants, though nonfunctional, did not appear altered in stability compared to the wild-type.

Adenosine Diphosphate↗

Toward a statistically relevant calibration end point for prostate seed implants.

Interstitial brachytherapy for carcinoma of the prostate is achieved through the use of a configuration of radioactive seeds placed in a manner that delivers a customized, reasonably uniform dose to the target volume. Accurate dose delivery depends on both precise seed placement and reliable seed strength in the implanted configuration. This study assumes the independence of the two issues, and quantifies the reduction in the minimum dose to the surface of the gland due only to variability in individual seed strengths. Current AAPM guidelines pertaining to the acceptable limits on seed-to-seed variability are prudent for small configurations of seeds, yet are likely to be overly stringent for applications such as prostate seed implantation. In this study we determine the reduction in the minimum peripheral dose (mPD) caused by the introduction of source strength variability, and provide statistical insight into this effect. It is concluded that the current guidelines limit the reduction in mPD to < or =0.4% relative to the prescription value, for an average configuration, due to the inclusion of strength variability. The maximum observed reduction in mPD would be < or =1.5%. This value is an order of magnitude lower than the recommendations of the AAPM Task Group 40 for the overall accuracy of brachytherapy procedures, which suggests that seed strength variability is of limited concern and that constraints on this factor should perhaps be reevaluated.

Biophysical Phenomena↗

Architectural transcription factors and the SAGA complex function in parallel pathways to activate transcription.

Recent work has shown that transcription of the yeast HO gene involves the sequential recruitment of a series of transcription factors. We have performed a functional analysis of HO regulation by determining the ability of mutations in SIN1, SIN3, RPD3, and SIN4 negative regulators to permit HO expression in the absence of certain activators. Mutations in the SIN1 (=SPT2) gene do not affect HO regulation, in contrast to results of other studies using an HO:lacZ reporter, and our data show that the regulatory properties of an HO:lacZ reporter differ from that of the native HO gene. Mutations in SIN3 and RPD3, which encode components of a histone deacetylase complex, show the same pattern of genetic suppression, and this suppression pattern differs from that seen in a sin4 mutant. The Sin4 protein is present in two transcriptional regulatory complexes, the RNA polymerase II holoenzyme/mediator and the SAGA histone acetylase complex. Our genetic analysis allows us to conclude that Swi/Snf chromatin remodeling complex has multiple roles in HO activation, and the data suggest that the ability of the SBF transcription factor to bind to the HO promoter may be affected by the acetylation state of the HO promoter. We also demonstrate that the Nhp6 architectural transcription factor, encoded by the redundant NHP6A and NHP6B genes, is required for HO expression. Suppression analysis with sin3, rpd3, and sin4 mutations suggests that Nhp6 and Gcn5 have similar functions. A gcn5 nhp6a nhp6b triple mutant is extremely sick, suggesting that the SAGA complex and the Nhp6 architectural transcription factors function in parallel pathways to activate transcription. We find that disruption of SIN4 allows this strain to grow at a reasonable rate, indicating a critical role for Sin4 in detecting structural changes in chromatin mediated by Gcn5 and Nhp6. These studies underscore the critical role of chromatin structure in regulating HO gene expression.

Acetyltransferases↗

The inclusion compounds of beta-cyclodextrin with 4-substituted benzoic acid and benzaldehyde drugs studied by proton nuclear magnetic resonance spectroscopy.

Inclusion compounds of some 4-substituted benzoic acid and benzaldehyde drugs with beta-cyclodextrin were prepared and characterized by IR spectroscopy, powder X-ray diffraction, thermogravimetry, and 1H-NMR spectroscopy. The thermal stability and chemical stability of these drugs were strikingly improved after inclusion. The effect of inclusion on the chemical-shifts of protons H-3 and H-5 in the NMR spectroscopy is discussed. Using the relative shift theory, the preferred inclusion mode was proposed. The center of the aromatic ring of the drug molecule was considered to be located in the cavity 1.2 A inside from the H-5 plane of beta-cyclodextrin.

Algorithms↗

Design of a novel membrane-destabilizing peptide selectively acting on acidic liposomes.

The design of amphipathic peptides resulted in a novel peptide with a selective ability to destabilize lipid bilayers of acidic liposomes. The newly synthesized peptide, termed mast 21, is a 21-residue long amino acid chain and can only act effectively on acidic liposomes lacking cholesterol. Moreover, mast 21 killed gram-positive and gram-negative bacteria, and it had no hemolytic activity. The antimicrobial and hemolytic activities paralleled the results of membrane destabilizing activity using liposomes. Circular dichroism and Trp-fluorescence emission spectra showed changes in the peptide conformation and circumstances around the peptide during interaction with liposomes. These changes were consistent with an increased alpha-helical content and a less polar environment for the tryptophan residue of the peptide. Mast 21 was observed under dark-field microscopy in real time attacking liposomes. Acidic liposomes were attacked, which resulted in peeling of the lipid bilayer with its subsequent destruction.

Amino Acid Sequence↗

Prevention of albuminuria by aminoguanidine or ramipril in streptozotocin-induced diabetic rats is associated with the normalization of glomerular protein kinase C.

This study examined whether the prevention of diabetes-related albuminuria by aminoguanidine (AG) or ramipril (RAM) may be mediated by a common post-glomerular basement membrane renal intracellular mechanism involving protein kinase C (PKC). The renal handling of albumin was examined over 24 weeks in control and streptozotocin (STZ)-induced diabetic rats. A radioimmunoassay (RIA) that measures intact albumin, and intravenously injected tritium-labeled rat serum albumin, was used to assess the proportion of intact albumin and albumin fragments in urine. Diabetes was induced in male Sprague-Dawley rats by the intravenous administration of STZ at a dose of 50 mg/kg. Age-matched control rats received buffer alone. Diabetes was characterized by an increase in blood glucose (>15 mmol/l), an increase in GHb (means at 24 weeks 29.3+/-1.1%; control 6.1+/-0.1%, P<0.005), an increase in glomerular filtration rate (GFR) (4.13+/-0.15 ml/min; control 3.54+/-0.19 ml/min, P<0.005), an increase in intact albumin excretion rate (expressed as geometric mean 11.64 times/divided by 2.11 mg/24 h; control 0.74 times/divided by 1.57 mg/24 h, P<0.005) as measured by RIA, and an increase in glomerular PKC activity (26.83+/-2.38 pmol x mg(-1) x min(-1); control 14.6+/-2.99 pmol x mg(-1) x min(-1), P<0.005). Treatment of diabetic rats with either AG or RAM prevented the rise in intact albuminuria and glomerular PKC activity. Renal lysosomal cathepsin activity decreased in diabetic rats and this was not prevented by AG or RAM. Neither drug affected glycemic control or GFR, but RAM reduced systolic blood pressure (BP), whereas AG did not. These data indicate that urinary excretion of intact albumin and albumin-derived fragments in diabetes may be modulated independently of glycemic control (AG and RAM) and systolic BP (RAM). While both drugs are known for their different mechanisms of action, the fact that both prevent diabetes-related increases in glomerular PKC activity and albuminuria supports the hypothesis that PKC plays a central role in the development of diabetic nephropathy.

Albuminuria↗

Prognostic role of K-ras in patients with progressive colon cancer who received treatment with Marimastat (BB2516).

We determined the prognostic role of K-ras mutation in tumor tissue of patients with refractory colon cancer who received Marimastat (BB2516). DNA was extracted from paraffin-stored tumor tissue of 27 patients who previously failed 5-fluorouracil and were treated with BB2516. The presence of K-ras mutation was characterized by Polymerase Chain Reaction using ras- and p53-specific primers. ras and p53 oncoprotein expression was analyzed by an automated biotin-avidin immunoproxidase technique. Seventeen patients had a normal K-ras sequence and 10 patients had a K-ras mutation. Median survival of patients with a normal ras sequence was 330 days from the time of BB2516 treatment compared with 160 days for patients with a K-ras mutation (p = 0.0442, Wilcoxon; 0.0130 Log-Rank). No differences in age, sex, cancer stage, surgical treatment, or chemotherapy treatment were observed. Abnormalities involving ras expression did not affect survival. By comparison, median survival for patients with p53 mutation or p53 overexpression was both 158 days after BB2516 treatment. Patients having both K-ras and p53 mutations had the poorest median survival of 113 days (p = 0.035). There is a suggestion by univariate analysis that the presence of a K-ras mutation may predict survival in patients with progressive colon cancer. Further assessment with larger patient numbers and multivariate analysis is indicated.

Adult↗

A novel immunoadsorbent for rheumatoid arthritis therapy--preparation and efficacy evaluation.

AIM: To develop a novel immunoadsorbent for rheumatoid arthritis (RA) therapy. METHODS: A RA immunoadsorbent was developed by binding heat-aggregated human IgG(HAHIgG) to porous agar gel beads. Its adsorption capacity for rheumatoid factors (RFs), storage stability and blood compatibility were evaluated. RESULTS: The coupling yield of HAHIgG on the carrier was 6.0 mg/g wet gel. Saturation adsorption capacity of the adsorbent for IgMRF, IgGRF and IgARF were 3400, 2240 and 2400 IU/g, respectively. The adsorbent can be stored at 4 degrees C for three months without significant variance in its activity. Its fine permeability and hemocompatibility were demonstrated by extracorporeal hemoperfusion on rabbits. CONCLUSION: HAHIgG/agar gel is a safe and effective immunoadsorbent for RA therapy, its potential clinical use is promising in the future.

Agar↗

Adsorption of bilirubin by amine-containing crosslinked chitosan resins.

Crosslinked chitosan resin, which has good blood compatibility, was prepared by crosslinking chitosan solution with glutaraldehyde. Polymeric adsorbents for bilirubin have been synthesized by chemical modification of crosslinked chitosan resins with di-, tri-, tetra-, and pentammines. The adsorption of bilirubin on the adsorbents was investigated in detail. The results indicated that electrostatic interaction and hydrophobic interactions are the main driving forces for the adsorption. Compared with crosslinked chitosan resin, the functionalized chitosan beads have higher adsorption capacity for unconjugated and conjugated bilirubin.

Adsorption↗

Differential distribution of the neuron-associated class III beta-tubulin in neuroendocrine lung tumors.

OBJECTIVE: To study the immunoreactivity profile of the neuron-associated class III beta-tubulin isotype (beta III) in epithelial lung tumors. DESIGN: One hundred four formalin-fixed, paraffin-embedded primary and metastatic lung cancer specimens were immunostained with an anti-beta III mouse monoclonal antibody (TuJ1) and an anti-beta III affinity-purified rabbit antiserum. Paraffin sections from fetal, infantile, and adult nonneoplastic lung tissues were also examined. RESULTS: In the fetal airway epithelium, beta III staining is detected transiently in rare Kulchitsky-like cells from lung tissues corresponding to the pseudoglandular and canalicular but not the saccular or alveolar stages of development. beta III is absent in healthy, hyperplastic, metaplastic, and dysplastic airway epithelium of the adult lung. In contrast, beta III is highly expressed in small cell lung cancer, large cell neuroendocrine carcinoma, and in some non-small cell lung cancers, particularly adenocarcinomas. There is no correlation between expression of beta III and generic neuroendocrine markers, such as chromogranin A and/or synaptophysin, in pulmonary adenocarcinomas. Also, focal beta III staining is present in primary and metastatic adenocarcinomas (to the lung) originating in the colon, prostate, and ovary. beta III is expressed to a much lesser extent in atypical carcinoids and is rarely detectable in typical carcinoids and squamous cell carcinomas of the lung. The distribution of beta III in small cell lung cancer and adenocarcinoma metastases to regional lymph nodes and brain approaches 100% of tumor cells, which is substantially greater than in the primary tumors. CONCLUSIONS: In the context of neuroendocrine lung tumors, beta III immunoreactivity is a molecular signature of high-grade malignant neoplasms (small cell lung cancer and large cell neuroendocrine carcinoma) although its importance in atypical carcinoids must be evaluated further. In addition, beta III may be a useful diagnostic marker in distinguishing between small cell lung cancers and certain non-small cell lung cancers (poorly differentiated squamous cell carcinomas), especially in small biopsy specimens. To our knowledge, beta III is the only tumor biomarker that exhibits a substantially more widespread distribution in poorly differentiated than in better differentiated pulmonary neuroendocrine tumors. However, the significance of beta III phenotypes in non-small cell lung cancer, particularly adenocarcinoma, with respect to neuroendocrine differentiation and prognostic value, requires further evaluation.

Adult↗

Synergistic interaction between anti-p185HER-2 ricin A chain immunotoxins and radionuclide conjugates for inhibiting growth of ovarian and breast cancer cells that overexpress HER-2.

Radionuclide conjugates or ricin A chain (RTA) immunotoxins that target pl85HER-2 have partially inhibited the growth of human ovarian cancer xenografts in athymic mice but generally have not cured mice bearing human tumor transplants. The present study was undertaken to explore whether a combination of ionizing radiation and an immunotoxin could exert additive or synergistic cytotoxicity in culture and in vivo against cancer cells that overexpress p185HER-2. In cell culture, treatment with 200-2000 cGy external beam irradiation followed by incubation with TA1-anti-pl85mHER2-RTA immunotoxin (TA1-RTA) produced synergistic inhibition of clonogenic growth of ovarian and breast cancer cells that expressed > 10(6) pl85HER-2 receptors/cell. The effect on cell survival correlated with an inhibition of DNA repair. A prior study (F. J. Xu et al, Nucl. Med. Biol., 24: 451-460, 1997) compared the biodistribution of radionuclide conjugates prepared with monoclonal antibodies that bind to different epitopes on the extracellular domain of pl85HER-2 and found optimal tumor uptake with the 520C9 antibody, which did not compete with TA1 for binding to the receptor. In this report, the TA1-RTA immunotoxin and the 131I-labeled 520C9 radionuclide conjugate could each inhibit the growth of clone-9002-18 xenografts in athymic mice but did not yield long-term survivors using maximally tolerated doses of each agent. When TA1-RTA and 131I-labeled 520C9 were used in combination, a greater inhibition of tumor growth was obtained than with either single agent. Similarly, survival with the combined treatment was significantly prolonged (P = 0.004) relative to treatment with immunotoxin or radionuclide conjugate alone. After treatment with an optimal combination of immunotoxin and radionuclide conjugate, 50% of mice survived >300 days, whereas controls succumbed with a median survival of 36 days. These results suggest that combinations of immunotoxins and radionuclide conjugates deserve further evaluation for the treatment of cancers that overexpress pl85HER-2.

Animals↗

[The study of expression and distribution of PCNA in hypertrophic scar tissue].

OBJECTIVE: To analyze the expression and the distribution of proliferation cell nuclear antigen (PCNA) in hypertrophic scar for identifying its certain characteristics during the fibroblast proliferation. METHODS: Bioptic samples were taken form 12 cases of hypertrophic scar, 8 cases of matured scars and 20 cases of controlled normal skin. Each sample was immunohistochemically stained and examined with monoclonal antibody[PCNA(pc10)] technique. The level of PCNA expression was decided for evaluation of the fibroblast proliferation. RESULTS: The level of PCNA in the hypertrophic scar(45.4 +/- 12.3) was significantly higher than mature scar(17.4 +/- 6.2), also normal skin(13.5 +/- 4.1, P < 0.01). But, there was no significant deference between the matured scar and the normal skin. The PCNA intracellular particles may sometimes be bound in the keratinocytes and the fibroblasts of some connective tissue. CONCLUSION: The fibroblast proliferation in the hypertrophic scar has kept a high level. During the process of hypertrophic scar formation it may play an important role.

Adolescent↗

[Long-term monitoring of artificial vagina reconstructed with sigmoid colon].

OBJECTIVE: To observe the influence of the artificial plastic vagina on overall patient health. METHODS: Length and width of the artificial vagina were measured. Histological studies were performed under light and electron microscope. Vaginal bacterial flora were analyzed using the drop-implant method. Vaginal HPV and ER were detected with ABC histochemical staining. RESULTS: According to the results of anatomic measurements, artificial vagina was similar to normal vagina. The reductions of glands in the mucosa and collagen fibers as well as interstitial tissue hyperplasia in the lower segment of artificial vagina were documented. Four kinds of bacteria indigenous to the sigmoid colon were found in artificial vagina and were studied microbiologically with only differences in the amount and detection rates of bacteria flora. The positive presentation of HPV was not significantly different from that in the control group. The positive presentation of estrogen receptor (ER) in the epithelium of artificial vagina was not found. CONCLUSION: The reconstruction of artificial vagina with sigmoid colon is a safe, effective and satisfactory procedure for the patient.

Adolescent↗

[The study of histopathology and bacteriology of coronal pulp tissue in deciduous teeth with deep dentin caries].

OBJECTIVE: To study the status of coronal pulp of deciduous teeth with deep caries and causes of pulpal histopathological changes. METHODS: 45 deciduous molars with occlusal deep caries were selected at random. The patients did not receive any antibiotic for one month. The coronal pulpal histopathology was observed with optical microscopic technique. The bacteria in pulp chamber were cultured by the ways of aerobic and anaerobic culture technique. The dentinal tubular structures and bacteria within the tubules of cavity basal part dentin were studied with scanning electron microscopic technique. RESULTS: Coronal pulp tissue of 77.8% of deciduous teeth with deep caries showed chronic inflammation to various degrees or chronic pulpitis with acute attack. There were aerobic and anaerobic mixed infection in pulp chambers of 94.9% deciduous teeth with deep caries. It was found that coccus and bacillus invaded into dentinal tubules of cavity basal part. Coccus located inside tubules with intact tubular walls, while tubular walls were destroyed the bacillus was present. CONCLUSION: There are aerobic and anaerobic mixed infection in pulp chamber of deciduous teeth with deep caries. The coronal pulp tissue shows chronic inflammation to various extent in over 2/3 deciduous teeth with deep caries. Bacillus has stronger destructive power to dental tubules.

Child↗

[Study on relationship of parameters of nitric oxide, endothelin and blood stasis syndrome in traditional Chinese medicine in acute cerebral infarction].

OBJECTIVE: To explore the relationship of parameters of nitric oxide (NO), endothelin (ET) and blood stasis syndrome (BSS) of traditional Chinese medicine (TCM) in acute cerebral infarction (ACI). METHODS: Seventy-three patients of ACI (ACI group) were divided into two groups by the score of BSS: BSS group (included 18 cases of serious BSS, 19 cases of moderate BSS, and 21 cases of mild BSS); and non-BSS group (15 cases); while 30 healthy subjects were taken as the control group, their NO and ET were determined. RESULTS: Compared with the control group, the level of ET and ratio of ET/NO raised significantly in the ACI group and the BSS group (P < 0.01). The levels of ET and ratio of ET/NO of mild, moderate and serious BSS increased in order, but only the serious BSS in comparing with mild, moderate group of BSS had significant difference (P < 0.01). The NO levels of ACI group, non-BSS group in comparing with healthy control, there was significant decrease (P < 0.05, P < 0.01). The NO concentration among the mild, moderate and serious group of BSS had insignificant difference (P > 0.05). CONCLUSION: NO and ET participates the formation and development of ACI, owing to the disturbed NO and ET secretion by vascular, nerve cells etc., these might be the pathologic basis of BSS occurrence.

Acute Disease↗

[Tachycardia ameliorated by electroacupuncture in morphine withdrawal rats].

OBJECTIVE: To establish morphine withdrawal tachycardia model of rat and to observe the effect of electroacupuncture (EA) with different frequency on its heart rate. METHODS: Morphine dependence was induced in Wistar rats by injection of morphine for 8 days successively, and EA 1 mA in strength was given after withdrawal of morphine with different frequencies of 2 Hz, 15 Hz and 100 Hz, the heart rate and blood pressure were recorded in the awaked rats. RESULTS: Morphine abstinent rats showed a 24% increase of heart rate as compared with that of the normal control group, but no significant change was observed in blood pressure. The 100 Hz and 15 Hz EA produced a 13.4% and 13.1% decrease of heart rate respectively, whereas 2 Hz EA produced insignificant change. CONCLUSION: The reducing effect of percutaneous electric stimulation on tachycardia in heroin addicts revealed clinically can be replicated in the rat model.

Animals↗