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Biomedical subjects

R Huang

Publications and source records attributed to R Huang.

At least 19 recordsLinked to original sources

Expression pattern of BMPs during chick limb development.

In vertebrates, BMPs (bone morphogenic proteins) play critical roles in establishing the basic embryonic body plan and are involved in the development of a large variety of organs and tissues. Here, we analyzed the expression pattern of various BMPs (2, 4, 5 and 7) by whole mount in situ hybridization during chick limb development. In limb, expression of BMPs suggests evolutionary conserved mechanisms of BMP-dependent differentiation between lower and higher vertebrates. During the early developmental stages, BMP-2 and BMP-7 are expressed in the posterior distal mesenchyme leaving a less prominent expression anteriorly. BMP-4 is initially expressed in the anterior mesenchyme and spreads later to the whole mesenchyme leaving a stronger expression at the anterior side. From HH-stage 25, expression of BMP-4 is observed in the anterior-posterior margins of the limb bud. The BMPs 2, 4 and 7 are expressed strongly in the AER, whereas BMP-5 is expressed as a weak signal in the distal mesoderm during the early stages of limb development. Later from HH-stage 25 onwards, BMP-5 is expressed in the dorsal and ventral muscular mass of the developing limb. As digits become identifiable, expression of BMPs are observed in the interdigital mesenchyme and can also be detected along the contours of the developing phalanges and at the distal tips of the digits. All these BMPs are found to be expressed in the developing feather buds from day 8 onwards.

Animals↗

Complete ultrasonic transducer characterization and its use for models and measurements.

Transmitting and receiving properties of ultrasonic piezoelectric crystal transducers that directly affect the measured output voltage in an ultrasonic measurement system are described. These transducer properties are the transducer's electrical impedance and sensitivity, the transducer's radiation impedance, and the transducer's effective parameters (effective radius and focal length). It is shown that all these properties can be obtained with a series of calibration measurements, most of them purely electrical in nature. This series of measurements is described, including a newly developed method that makes the determination of the transducer sensitivity simpler than with previous methods. It is demonstrated that by combining these transducer properties with knowledge of the electrical properties of the pulser/receiver and cabling and the acoustic/elastic processes present in an ultrasonic measurement system, it is possible to accurately simulate the output voltage of the system.

Journal Article↗

Improving the Born approximation for the scattering of ultrasound in elastic solids.

It has recently been demonstrated that the Born approximation for predicting the scattering response of flaws can be improved through the use of simple modifications called the "doubly distorted Born approximation". In this paper the doubly distorted Born approximation itself is modified with phase and amplitude corrections that further improve the Born scattering results for isotropic elastic media. The reliability of this new modification of the Born approximation has been evaluated by comparison with the exact solution for spherical inclusions obtained with the method of separation of variables. Unlike the ordinary Born approximation which works well only for very weak scattering inclusions, our modification of the doubly distorted Born approximation gives improved scattering results for both weak and strong scattering inclusions.

Journal Article↗

Effect of age on outcomes after left ventricular assist device placement.

The influence of age on outcomes after left ventricular assist device (LVAD) implantation is not well studied. To address this question, we assessed 222 patients who underwent LVAD placement and were divided into quartiles based on age (years): group 1, or=60. Eighty-four patients died on LVAD support. Six- and 12-month survivals for the four groups of LVAD patients were 67.7, 73.7, 49.8, and 38.2, and 49.4, 57.3, 42.7, and 26.2, respectively (all P<.01). Older patients showed a higher risk of infections, embolic strokes, and respiratory complications. They were the least likely to undergo reoperations postimplantation (56%, 53%, 50%, 46%, P=.06). After adjusting for baseline differences between the groups, there was a trend toward increasing mortality with age, which did not reach significance (odds ratio 1.93; 95% confidence interval 0.95 to 3.92 for the oldest quartile as compared with the youngest). In conclusion, these results suggest in the absence of other high risk factors, age alone should not be used as an independent contraindication for LVAD implantation.

Adult↗

Anemia in heart failure may warrant more aggressive listing for cardiac transplantation.

Peak exercise oxygen consumption (VO2, in mL/min/kg) is a reliable prognostic marker in heart failure (HF). Anemia, which is common in HF, affects both exercise capacity and prognosis. In this study, we assessed the relationship between peak VO2 and prognosis among HF patients with and without anemia. Data on 344 HF patients were divided into three groups based on peak VO2 (<10, 10 to 14, and >14). Each group stratified by the presence of anemia (<13 mg/dL in men and <12 mg/dL in women) was compared for death or left ventricular assist device (LVAD) placement, and death or LVAD or transplantation. The mean patient age was 53.4+/-11.8 years; hemoglobin level, 12.8+/-1.8 mg/dL; and average follow-up, 629+/-459 days. Overall 32% of patients were anemic. The presence of anemia significantly impacted outcomes among patients with peak VO2<10, namely 42.2% versus 18.9% death or LVAD need (P=.01) and 66.7% versus 43.3% death or LVAD or transplantation (P=.06) for anemic versus nonanemic patients, respectively. The prognosis was similar among groups with higher peak VO2. After adjusting for baseline differences, anemic patients with peak VO2<10 were at higher risk for adverse outcomes: odds ratio (OR) 3.69 (95% confidence interval [95% CI] 1.31 to 9.87) for death or LVAD; and OR 5.67 (95% CI=1.42 to 19.4) for death or LVAD or transplant. Anemia significantly impacted the prognosis of HF patients with peak VO2 less than 10 mL/min/kg. Since these patients are most likely to be evaluated for transplantation, the presence of anemia may further help to stratify prognosis in this group.

Adult↗

Lipid-laden macrophage index in healthy canines.

BACKGROUND: The quantity of lipids in alveolar macrophages is used clinically as an indicator of aspiration, which is associated with increased lung inflammation. This is determined in the macrophages obtained from bronchoalveolar lavage (BAL) and is expressed as lipid-laden macrophage index (LLMI). Although there is ample data on LLMI in human subjects, there is no published data pertaining to the baseline measures of the LLMI in canines, which are extensively used for experimental studies on gastroesophageal reflex (GER) and airway diseases. Primary aim of the present study was to collect data pertaining to the cytology and LLMI in BAL fluids obtained from healthy dogs. MATERIALS AND METHODS: Eight dogs underwent a bronchoscopy with BAL collection, and esophageal pH monitoring to determine the reflux index (RI). The BAL fluid was processed and reviewed under a microscope to determine the proportions of the various cell types and the LLMI. RESULTS: The median RI among the subjects was found to be 0.6 (0.0, 1.2). The BAL cytology analysis showed 77.5% (71.0, 83.5) macrophages, 21.0 (13.0, 24.5) lymphocytes and 2.5 (1.5, 5.0) neutrophils. The median LLMI was found to be 156 (111, 208). CONCLUSIONS: Although the differential cell counts in the dogs' BAL fluid was comparable to that of other experimental animals and humans, the LLMI was distinctly higher than the corresponding value reported for other species. As LLMI is a valuable modality for evaluation of intrapulmonary pathophysiology, these data on LLMI can be used as a species-specific standard for canine subjects used for experimental studies on GER and airway diseases.

Animals↗

CYP19 haplotypes increase risk for Alzheimer's disease.

Cytochrome P450 aromatase, an enzyme that catalyses the conversion of androgens to oestrogen, is expressed at high levels in the gonads and in the brain. Aromatase activity is increased in the nucleus basalis of Meynert during aging and in Alzheimer's disease (AD), making the gene (CYP19), at 15q21.1, a potential candidate risk factor. We examined 18 single nucleotide polymorphisms spanning the 5'-untranslated region and the entire coding region of CYP19 in 227 patients with AD and 131 control spouses. We found that the gene region could be divided into two haplotype blocks; a haplotype in block 1 and a haplotype in block 2 increased the risk of developing the disease by twofold in APOE 4 carriers. The implication of two haplotypes conferring increased risk for AD warrants further investigation of the regulation of aromatase activity in brain.

Aged↗

Cystatin C as a risk factor for Alzheimer disease.

Cystatin C, a protease inhibitor with widespread distribution, is upregulated in response to injury. Levels are elevated in the brains of patients with Alzheimer disease (AD). We compared frequencies for the CST 3 exon 1 polymorphism in patients with AD and controls. A proportional odds model indicated that the CST 3 A and APOE4 combination carried a high risk: a 14-fold elevation for men and 16-fold for women. These risks apply to risk at ages older than 64 years and to a shift in onset to ages younger than 65 years.

Age of Onset↗

Linking pathway gene expressions to the growth inhibition response from the National Cancer Institute's anticancer screen and drug mechanism of action.

Novel strategies are proposed to quantitatively analyze and relate biological pathways to drug responses using gene expression and small-molecule growth inhibition data (GI(50)) derived from the National Cancer Institute's 60 cancer cells (NCI(60)). We have annotated groups of drug GI(50) responses with pathways defined by the Kyoto Encyclopedia of Genes and Genomes (KEGG) and BioCarta, and functional categories defined by Gene Ontology (GO), through correlations between pathway gene expression patterns and drug GI(50) profiles. Drug-gene-pathway relationships may then be utilized to find drug targets or target-specific drugs. Significantly correlated pathways and the gene products involved represent interesting targets for further exploration, whereas drugs that are significantly correlated with only certain pathways are more likely to be target specific. Separate pathway clustering finds that pathways engaged in the same biological process tend to have similar drug correlation patterns. The biological and statistical significances of our method are established by comparison to known small-molecule inhibitor-gene target relationships reported in the literature and by standard randomization procedures. The results of our pathway, gene expression and drug-induced growth inhibition associations, can serve as a basis for proposing testable hypotheses about potential anticancer drugs, their targets, and mechanisms of action.

Antineoplastic Agents↗

Purification, characterization, and crystallization of the components of the nitrobenzene and 2-nitrotoluene dioxygenase enzyme systems.

The protein components of the 2-nitrotoluene (2NT) and nitrobenzene dioxygenase enzyme systems from Acidovorax sp. strain JS42 and Comamonas sp. strain JS765, respectively, were purified and characterized. These enzymes catalyze the initial step in the degradation of 2-nitrotoluene and nitrobenzene. The identical shared reductase and ferredoxin components were monomers of 35 and 11.5 kDa, respectively. The reductase component contained 1.86 g-atoms iron, 2.01 g-atoms sulfur, and one molecule of flavin adenine dinucleotide per monomer. Spectral properties of the reductase indicated the presence of a plant-type [2Fe-2S] center and a flavin. The reductase catalyzed the reduction of cytochrome c, ferricyanide, and 2,6-dichlorophenol indophenol. The ferredoxin contained 2.20 g-atoms iron and 1.99 g-atoms sulfur per monomer and had spectral properties indicative of a Rieske [2Fe-2S] center. The ferredoxin component could be effectively replaced by the ferredoxin from the Pseudomonas sp. strain NCIB 9816-4 naphthalene dioxygenase system but not by that from the Burkholderia sp. strain LB400 biphenyl or Pseudomonas putida F1 toluene dioxygenase system. The oxygenases from the 2-nitrotoluene and nitrobenzene dioxygenase systems each had spectral properties indicating the presence of a Rieske [2Fe-2S] center, and the subunit composition of each oxygenase was an alpha(3)beta(3) hexamer. The apparent K(m) of 2-nitrotoluene dioxygenase for 2NT was 20 muM, and that for naphthalene was 121 muM. The specificity constants were 7.0 muM(-1) min(-1) for 2NT and 1.2 muM(-1) min(-1) for naphthalene, indicating that the enzyme is more efficient with 2NT as a substrate. Diffraction-quality crystals of the two oxygenases were obtained.

Comamonadaceae↗

Functional interaction between APOE4 and LDL receptor isoforms in Alzheimer's disease.

BACKGROUND: Multiple genes have been provisionally associated with Alzheimer's disease, including the coding polymorphisms in exons 8 and 13 in the low density lipoprotein receptor gene (LDLR), situated on chromosome 19p13.2. METHODS: The sample groups consisted of 180 AD patients and 141 control spouses. We carried out genotyping of LDLR8 and LDLR13. RESULTS: The LDLR8 GG genotype was common, found in 84% of the unaffected control subjects and 91% of the AD patients in our study. There was a ninefold elevation in risk associated with GG:CC versus A- and T- among APOE4+ subjects when compared with APOE4- subjects (odds ratio 9.3; 95% confidence interval 1.8 to 48.2). With the additional information on LDLR polymorphism, we defined an overall 12 fold elevation in risk for APOE4 in combination with LDLR GG:CC (11.9; 2.8 to 50.0; Fisher's exact test, p = 0.0002; standard power 0.999), compared with other subjects lacking all three of these polymorphisms. CONCLUSION: These results imply a functional interaction between ApoE and LDL receptor proteins that determines risk for Alzheimer's disease.

Aged↗

The role of Emx2 during scapula formation.

The scapula is subdivided into head, collum, and blade. Due to the expression pattern of Emx2 and the absence of the scapula blade in Emx2 knockout mice, it has been suggested that Emx2 is involved in the formation of the scapula. Micromanipulation experiments revealed that ectoderm ablation over the somites does not affect Emx2 expression but inhibits the formation of the scapula blade indicating that Emx2 is not sufficient to induce scapula blade formation. Furthermore, we show that the formation of the scapula head is dependent, scapula blade formation independent of FGFR-1-mediated signaling. Overexpression of Emx2 does not influence scapula blade formation but leads to the development of an additional posterior digit in the anterior border of the limb. Taken together, the data presented implicate that Emx2 expression is necessary but not sufficient for the development of the scapula blade. It is not a marker for scapula development but rather provides positional information along the proximodistal and anterior-posterior limb axes, whereas the specificity of the developing skeletal elements is determined by the concerted interaction of Emx2 with other factors.

Animals↗

Control of the temporal and spatial Uncx4.1 expression in the paraxial mesoderm of avian embryos.

Uncx4.1 is a homeobox containing transcription factor that determines the development of the pedicles of the neural arches, transverse processes and proximal ribs. In this paper we characterize the expression pattern of Uncx4.1 during chick embryogenesis with special focus on its expression in the paraxial mesoderm. In the presomitic mesoderm, Uncx4.1 is expressed in the caudal halves of the somites I and II. In the newly formed somites, Uncx4.1 expression remains in the caudal somite halves but becomes restricted to the somitocoele and the ventral epithelial wall. After somite compartmentalization, Uncx4.1 is expressed in the caudal half of the sclerotome in a well defined spatial and temporal pattern. Micromanipulations revealed that Uncx4.1 expression in the presomitic mesoderm is independent of signals from the axial structures and presumably induced by the intrinsic Notch/Delta driven oscillator activity that determines craniocaudal somite polarity. In contrast, in the maturing somite Uncx4.1 expression depends on signals from the axial structures. The notochord-floor plate complex is essential for maintaining Uncx4.1 expression in the caudal somite half. The neural tube is necessary for providing sufficient Uncx4.1 positive sclerotomal material to enable development of pedicles of the neural arches and transverse processes.

Animals↗

Expression pattern of VEGFR-2 (Quek1) during quail development.

The growth and maintenance of the blood and lymphatic vascular systems is to a large extent controlled by members of the vascular endothelial growth factor (VEGF) family via the tyrosine kinase receptors (VEGFRs) expressed in angioblastic cells. Here, we analyzed the Quek1 (VEGFR-2) expression pattern by whole mount in situ hybridization during quail development. During early embryogenesis, Quek1 expression was detected at the caudal end of the blastoderm and primitive streak and in the head paraxial mesoderm. In somites, expression was observed from HH-stage 9 onwards in the dorsolateral region of both the forming and recently formed somites. During somite maturation, expression persists in the lateral portion of the somitic compartments, the dermomyotome and the sclerotome. Additionally, a second expression domain in the maturing somite was observed in the medial part of the sclerotome adjacent to the neural tube. This expression domain extended medially and dorsally and surrounded the neural tube during later stages. In the notochord, expression was observed from HH-stage 23 onwards. In the limb bud, expression was initiated in the mesenchyme at HH-stage 17. During organogenesis, expression was detected in the pharyngeal arches and in the anlagen of the esophagus, trachea, stomach, lungs, liver, heart and gut. Expression was also seen in feather buds from day 7 onwards. Our results confirm the angiogenic potential of the mesoderm and suggest that VEGFR-2 expressing cells represent multiple pools of mesodermal precursors of the hematopoietic and angiopoietic lineages.

Animals↗

Preservation of fecal continence and bowel function after radical perineal and retropubic prostatectomy: a questionnaire-based outcomes study.

PURPOSE: To assess fecal incontinence rates and bowel function for radical perineal (RPP) or radical retropubic (RRP) prostatectomy patients and to compare them with a matched control group. METHODS: The bowel function domain of the Expanded Prostate Cancer Index Composite (EPIC) was mailed to 150 consecutive patients who had undergone RPP (79) or RRP (71) by the same surgeon (HJK) and an age-matched control group (75). RESULTS: Fecal incontinence and bowel dysfunction were statistically equivalent for the study groups. CONCLUSIONS: There is no difference in fecal incontinence rates or bowel function when comparing RPP patients to RRP or control patients.

Adult↗

Antibiotic activity of lectins from marine algae against marine vibrios.

Saline and aqueous ethanol extracts of marine algae and the lectins from two red algal species were assayed for their antibiotic activity against marine vibrios. Experimental studies were also carried out on the influence of environmental factors on such activity, using batch cultures. The results indicated that many of the saline extracts of the algal species were active and that the activity was selective against those vibrios assayed. The algal extracts were active against Vibrio pelagius and the fish pathogen V. vulnificus, but inactive against V. neresis. Algal lectins from Eucheuma serra (ESA) and Galaxaura marginata (GMA) strongly inhibited V. vulnificus but were inactive against the other two vibrios. The antibacterial activity of algal extracts was inhibited by pretreatment with various sugars and glycoprotein. Extracts of the two red algae, E. serra and Pterocladia capillacea, in saline and aqueous ethanol, inhibited markedly the growth rate of V. vulnificus at very low concentrations. Culture results indicated that metabolites active against V. vulnificus were invariably produced in P. capillacea over a wide range of temperature, light intensity, and nutritional conditions. Enhanced antibacterial activity occurred when P. capillacea was grown under higher irradiance, severe nutrient stress and moderate temperature (20 degrees C), reflecting the specific antibiotic characteristics of this alga. The strong antibiotic activity of lectins towards fish pathogenic bacteria reveals one of the important roles played by algal lectins, as well as the potential high economic value of those marine algae assayed for aquaculture and for biomedical purposes.

Anti-Bacterial Agents↗

[Epidermoid carcinomas of the anal canal treated with definitive radiation therapy in a series of 305 patients].

PURPOSE: To identify prognostic factors and treatment toxicity in a serie of epidermoid cancers of the anal canal without evident metastasis. PATIENTS AND METHODS: Between June 1972 and January 1997, 305 patients (pts) were treated with curative-intent radiation therapy (RT). The T-stages according to the 1987 UICC classification were: 26 T1, 141 T2, 104 T3, and 34 T4. There were 49 pts with nodal involvement at presentation. Pretreatment anal function scoring according to our in-house system was: 22 scored 0, 182 scored 1, 74 scored 2, 7 scored 3, 11 scored 4, and 9 not available pts. The treatment started with external beam RT (EBRT) in 303 pts (median dose: 45 Gy). After a rest period of 4 to 6 weeks, a boost of 20 Gy was delivered by EBRT in 279 pts and by interstitial 192Ir brachytherapy (Bcy) in 17 pts. Seven pts received only one course of EBRT (mean dose: 49.5 Gy) and 2 pts were treated with interstitial 192Ir Bcy alone (55 and 60 Gy, respectively). Concomitant chemotherapy (5-fluoro-uracil and either mitomycin C or cisplatin) was delivered to 19 pts. Mean follow-up was 103 months. RESULTS: At the end of RT local tumor clinical complete response (cCR) rate was 80%. Out of 61 non responders or local progressive tumors 27 (44%) were salvaged with abdominoperineal resection (APR). The rate of local tumor relapse (LR) was 12%. Out of 37 LTR, 20 (54%) were salvaged with APR and one with interstitial 192Ir Bcy. The orevall local tumor control (LC) rate with or without salvage local treatment was 84%. LC rate with a good anal function scoring (score 0 and 1) was 56.5%. Among 181/186 available pts who preserved their anus, 94% had a good anal function scoring. For a subgroup of 15 pts with length tumor <2 cm-N0, the LC rate after the end of RT was 100%, the LC rate with or without local salvage treatment was 100%, and among 13 available pts who preserved their anus, the anal function scoring was good in 12 pts (92%). The 10-years disease-free survival was 74%. After multivariate analysis, 3 independent predicting factors significantly influenced the disease-free survival: gap duration between 2 courses of RT (>38 days vs < or =38 days, P =0.0025), pretreatment anal function scoring (0 vs 1 vs 2 vs 3 vs 4, P =4.4 10(-6)), and cCR after the end of RT (no complete response vs complete response, P =2.5 10(-14)). CONCLUSION: We confirm excellent results with RT in T1 and T2 lesions. However, chemoradiotherapy should be prefered to improve survival free of colostomy with a good anal sphincter function for tumors more than or equal to 2 cm in length and locally advanced tumors.

Adult↗