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Biomedical subjects

P Chen

Publications and source records attributed to P Chen.

At least 55 records · Page 3Linked to original sources

Regulation of galanin-like peptide gene expression by pituitary hormones and their downstream targets.

Galanin-like peptide (GALP) mRNA is expressed in neurones of the hypothalamic arcuate nucleus and within pituicytes in the neurohypophysis. Several neuropeptides that are expressed in the arcuate nucleus participate in the neuroendocrine regulation of pituitary hormone secretion. Our objective was to determine the extent to which GALP might be a target for regulation by pituitary hormones or their downstream targets in the rat. The expression of GALP mRNA in the arcuate nucleus was reduced by hypophysectomy as determined by in situ hybridization. However, this did not appear to be attributable to the loss of either gonadal or adrenal steroids because castrated, ovariectomized and adrenalectomized rats had GALP mRNA expression that was indistinguishable from their respective controls. Next, we investigated the effects of growth hormone deficiency on GALP mRNA expression by studying dwarf rats and found that GALP gene expression was not different between dwarf rats and controls. We found that thyroidectomy led to a significant reduction in GALP mRNA expression compared to intact controls, and thyroidectomized rats implanted with thyroxine pellets had GALP mRNA expression that was similar to intact controls. Thus, the reduction of GALP mRNA expression seen in hypophysectomized animals may reflect, in part, a selective loss of thyroid hormone. We also found that the expression of GALP mRNA was increased in the neurohypophysis of lactating rats compared to nonlactating rats, whereas GALP mRNA expression in the arcuate nucleus was unaffected by lactation. This suggests that the induction of GALP gene expression in pituicytes is physiologically associated with activation of oxytocin and vasopressin secretion during lactation.

Adrenalectomy↗

Cataract surgery and subtype in a defined, older population: the SEECAT Project.

AIM: To describe the distribution of cataract subtypes present before surgery among a defined population of older, bilaterally pseudophakic individuals. METHODS: This was a cohort study of bilaterally pseudophakic individuals participating in the Salisbury Eye Evaluation (SEE), and their locally resident siblings. Subjects underwent slit lamp and retroillumination photography and grading using the Wilmer Cataract Grading System. For all individuals determined to be bilaterally pseudophakic, an attempt was made to determine for each eye the type(s) of cataract present before surgery, based on previous SEE photographs (for SEE participants) and/or medical records obtained from the operating ophthalmologist (for both SEE participants and their siblings). RESULTS: The mean age of 223 participants providing data in this study was 78.7 (SD 5.2) years, 19.3% of subjects were black and 60.1% female. The most common surgically removed cataract subtype in this population was pure nuclear (43.5%), followed by nuclear combined with posterior subcapsular cataract (PSC) (20.6%), and nuclear combined with cortical (13.9%); less common types were pure cortical (4.9%), pure PSC (4.5%), and PSC combined with cortical (2.7%). Factors such as sex and source of lens data (study photograph versus clinical record) did not significantly affect the distribution of lens opacity types, while PSC was significantly (p = 0.01) more common among younger people and nuclear cataract was significantly (p = 0.001) more common among white compared to black people. CONCLUSION: Epidemiological studies have suggested that the different subtypes of cataract are associated with different risk factors. As studies begin to identify new prevention strategies for cataract, it would appear likely that different strategies will be efficacious against different types of cataract. In this setting, it will be helpful to know which cataract types are most frequently associated with surgery. Among this older, majority white population, nuclear cataract showed a clear predominance among individuals having undergone surgery in both eyes. This may be contrasted with both clinic and population based studies of younger people, which have generally found PSC cataract to predominate.

Age Distribution↗

Self-assembly of the ionic peptide EAK16: the effect of charge distributions on self-assembly.

Amphiphilic peptides suspended in aqueous solution display a rich set of aggregation behavior. Molecular-level studies of relatively simple amphiphilic molecules under controlled conditions are an essential step toward a better understanding of self-assembly phenomena of naturally occurring peptides/proteins. Here, we study the influence of molecular architecture and interactions on the self-assembly of model peptides (EAK16s), using both experimental and theoretical approaches. Three different types of EAK16 were studied: EAK16-I, -II, and -IV, which have the same amino acid composition but different amino acid sequences. Atomic force microscopy confirms that EAK16-I and -II form fibrillar assemblies, whereas EAK16-IV forms globular structures. The Fourier transform infrared spectrum of EAK16-IV indicates the possible formation of a beta-turn structure, which is not found in EAK16-I and -II. Our theoretical and numerical studies suggest the underlying mechanism behind these observations. We show that the hairpin structure is energetically stable for EAK16-IV, whereas the chain entropy of EAK16-I and -II favors relatively stretched conformations. Our combined experimental and theoretical approaches provide a clear picture of the interplay between single-chain properties, as determined by peptide sequences (or charge distributions), and the emerging structure at the nano (or more coarse-grained) level.

Computer Simulation↗

The laparoscopic experience of surgical graduates in the United States.

BACKGROUND: Although laparoscopic surgery has become widespread during the past decade, no systematic study of the training needs exists. To obtain guidance for planning, we analyzed the national resident operative experience during the past 8 years. METHODS: The laparoscopic experiences of all surgical residents graduating between 1994 and 2001 were subjected to regression analysis. The laparoscopic volume of each trainee and change in ratio of laparoscopic/open operation over time were used to estimate the growth of individual laparoscopic operations in training programs. RESULTS: Laparoscopic surgery constituted only 5.7% of a trainee's total surgical experience in 1994, but comprised 13% by 2001. A resident completing training in 1994 performed 53 laparoscopic operations, of which 79% (42) were cholecystectomies. By 2001, a graduate performed 126 laparoscopic operations, of which 68% (86) were cholecystectomies. During the interim, most laparoscopic operations exhibited growth. Trainee experience in some newer operations has also increased steadily but at a much slower rate. CONCLUSIONS: This descriptive statistical survey of training experience yields a comprehensive picture of the laparoscopic capability of the young surgeon. The growth potential of some newer operations has also been measured. Using these data, guidelines can be drawn as to which operation programs should focus resources on training residents. Since competence depends on exposure, residency training alone may not provide sufficient depth to allow recent graduates to perform the newer operations independently.

Adult↗

Thermodynamic fundamental equation of contact lines: selection of independent variables.

In this work we review the development of the generalized theory of capillarity. When considering the theory of contact lines, we find that the theory developed by Boruvka and Neumann (BN) requires significant modifications. Their choice of parameters (independent variables) for a line is insufficient for formulating the fundamental equation. Furthermore, there are differential geometric constraints on these geometric parameters but not included in their analysis. As a result, their independent variables are in fact dependent. To describe the geometry of contact lines properly, we present a new set of parameters from the differential geometry viewpoint and subsequently give the fundamental equation for the thermodynamic system of contact lines.

Journal Article↗

Expression, structure-function, and molecular modeling of vitamin D P450s.

Although vitamin D(3) is a natural product of a sunlight-mediated process in the skin, the secosteroid's biological function is dependent upon specific cytochrome P450 enzymes that mediate the parent vitamin's bioactivation and inactivation. Cytochrome P450C1 (CYP27B1) is the regulatory rate-limiting enzyme that directs the bioactivation process through introduction of a C-1alpha hydroxyl group. The resultant 1,25-dihydroxyvitamin D(3) (1,25D) is the biologically active secosteroid hormone that directs the multitude of vitamin D-dependent actions involved with calcium homeostasis, cellular differentiation and growth, and the immune response. The circulating and cellular level of 1,25D is regulated through a coordinated process involving the hormone's synthesis and degradation. Central to the degradation and turnover of 1,25D is the regulatory multi-catalytic cytochrome P450C24 (CYP24) enzyme that directs the introduction of C-24R groups onto targeted 25-hydroxy substrates. Discussed in this article is the action of the rat CYP24 to catalyze the side-chain oxidation and cleavage of 25-hydroxylated vitamin D metabolites. Expression and characterization of purified recombinant rat CYP24 is discussed in light of mutations directed at the enzyme's active site.

25-Hydroxyvitamin D3 1-alpha-Hydroxylase↗

Concentration effect on the aggregation of a self-assembling oligopeptide.

Concentration is a key parameter in controlling the aggregation of self-assembling oligopeptides. By investigating the concentration effects, an aggregation mechanism of EAK16-II is proposed. Depending on the critical aggregation concentration (CAC) of EAK16-II, the oligopeptide aggregates into protofibrils through seeding and/or a nucleation process. Protofibrils then associate with each other to form fibrils. The CAC was found to be approximately 0.1 mg/ml by surface tension measurements. The nanostructures of aggregates were imaged and analyzed by atomic force microscopy. Globular and fibrillar aggregates were observed, and their dimensions were further quantified. To ensure that the aggregates were formed in bulk solution, light scattering (LS) measurements were conducted to monitor the fibril formation with time. The LS profile showed two different rates of aggregation depending on whether the peptide concentration was above or below the CAC. At high concentrations, the LS intensity increased strongly at early times. At low concentrations, the LS intensity increased only slightly. Our study provides information about the nature of the oligopeptide self-assembly, which is important to the understanding of the fibrillogenesis occurring in conformational diseases and to many biomedical engineering applications.

Binding Sites↗

Study of binding between protein A and immunoglobulin G using a surface tension probe.

Molecular interactions and binding are one of the most important and fundamental properties in the study of biochemical and biomedical systems. The understanding of such interactions and binding among biomolecules forms the basis for the design and processing of many biotechnological applications, such as bioseparation and immunoadsorption. In this study, we present a novel method to probe molecular interactions and binding based on surface tension measurement. This method complements conventional techniques, which are largely based on optical, spectroscopic, fluorescence polarization, chromatographic or atomic force microscopy measurements, by being definite in determining molecular binding ratio and flexible in sample preparation. Both dynamic and equilibrium (or quasi-equilibrium) information on molecular binding can be obtained through dynamic and equilibrium surface tension measurements. For an important pair of biological ligand and ligate, Protein A and immunoglobulin G (IgG), the existence of molecular interactions and the binding ratio of 1:2 have been determined unequivocally with the proposed surface tension method. These results are confirmed/supported by a mass balance calculation and spectrophotometry experiment. In addition, adsorption isotherms for Protein A and IgG separately at the air/water interface have been established with the dynamic surface tension measurements. The results show that the Langmuir isotherm equation can describe the adsorption data satisfactorily for both Protein A and IgG solutions.

Biosensing Techniques↗

PSA-NCAM is up-regulated during optic nerve regeneration in lizard but not in goldfish.

The addition of polysialic acid (PSA) to neural cell adhesion molecule (NCAM) facilitates axon growth. Here we use Western blots and immunohistochemistry to examine expression of PSA-NCAM during optic nerve regeneration. In lizard, retinal ganglion cell axons become transiently PSA-NCAM positive. By contrast, goldfish RGC axons are PSA-NCAM negative both in normal animals and throughout regeneration with the exception of a PSA-NCAM-positive fascicle arising from newly generated RGCs. Transient sialylation of NCAM in lizard may assist regeneration in the nonpermissive reptilian visual pathway and facilitate the reestablishment of a crude topographic map; down-regulation in the long term may contribute to the breakdown in topography. The lack of sialylation in goldfish presumably reflects the permissive nature of the substrate allowing axon regeneration and the successful reestablishment of a topographic map.

Animals↗

Yeast cell adhesion on oligopeptide modified surfaces.

Self-assembling oligopeptides are novel materials with potential bioengineering applications; this paper explores the use of one of these oligopeptides, EAK 16 II, for modifying the surface properties of cell-supporting substrates. To characterize the surface properties, thermodynamic measurements of liquid contact angle and surface free energy were correlated to atomic force microscopy (AFM) observations. A critical concentration of 0.1 mg/ml was found necessary to completely modify the surface properties of the substrate with EAK 16 II. Adhesion of a yeast cell, Candida utilis, was modified by the coating of EAK 16 II on both hydrophobic (plastic) and hydrophilic (glass) surfaces: Cell coverage was slightly enhanced on the glass substrate, but decreased significantly on the plastic substrate. This indicates that the yeast cell adhesion was mainly determined via hydrophobic interactions between the substrate and the cell wall. However, on the EAK 16 II modified glass substrate, surface roughness might be a factor in causing a slightly larger cell adhesion than that on bare glass. The morphology of adhered cells was also obtained with AFM imaging, showing a depression at the center of the cell on all substrates. Small depressions on the oligopeptide-coated surfaces and plastic substrate may indicate good water-retaining ability by the cell. There was no apparent difference in cell adhesion and morphology among cells obtained from lag, exponential and stationary growth phases.

Candida↗

Oxidative activation of acylguanidine prodrugs: intestinal presystemic activation in rats limits absorption and can be inhibited by co-administration of ketoconazole.

1. The disposition of acyl prodrugs was studied to improve the delivery of a guanidine-containing parent compound with poor membrane permeability and poor absorption. 2. The prodrugs were evaluated in vitro and in vivo for conversion to drug. Prodrugs were evaluated for hydrolytic or oxidative bioactivation in intestinal homogenate and rat liver S9 or microsomes. The disposition of the prodrugs in vivo was monitored in bile duct-cannulated rats. 3. Compounds with n-alkylacyl groups were efficiently bioactivated, but were hydrolysed before absorption. 4. Hydrolytic bioactivation could be blocked in vitro by branching in the alkyl chain. These compounds showed modest improvements in absorption, despite favourable permeability. Experiments with liver microsomes demonstrated efficient NADPH-dependent oxidative bioactivation, which was proposed to occur through a CYP-mediated side chain oxidation followed by cyclization and release of parent compound. Ketoconazole co-administration yielded approximately a twofold increase in absorption. 5. The hydrolytically stable prodrugs were successful in increasing absorption of parent drug and were efficiently bioactivated, but they did not yield increased systemic levels of drug.

Administration, Oral↗

Training on a visual task improves the outcome of optic nerve regeneration.

Optic nerve regeneration in a lizard, Ctenophorus ornatus, is dysfunctional despite survival of most retinal ganglion cells and axon regeneration to the optic tectum. The regenerated retino-tectal projection at 6 months has crude topography but by 1 year is disordered; visually-elicited behavior is absent via the experimental eye. Here, we assess the influence of training on the outcome of optic nerve regeneration. Lizards were trained to catch prey presented within the monocular field of either eye. One optic nerve was then severed and visual stimulation resumed throughout regeneration. In the trained group, presentation was restricted to the eye undergoing optic nerve regeneration; for the untrained group, the unoperated eye was stimulated. Pupil responses returned in trained but not in untrained animals. At 1 year, trained animals oriented to and captured prey; untrained animals demonstrated minimal orienting and failed to capture prey. Regenerated retino-tectal projections were topographic in the trained but not in the untrained group as assessed by in vitro electrophysiological recording and by carbocyanine dye tracing. In vitro electrophysiological recording during application of neurotransmitter antagonists to the tectum revealed that the level of GABAergic inhibition was modest in trained animals but elevated in the untrained group; responses were mainly AMPA-mediated in both groups. We conclude that training improves the behavioral outcome of regeneration, presumably by stabilizing and refining the transient retino-tectal map and preventing a build-up of tectal inhibition. The results suggest that for successful central nerve regeneration to occur in mammals, it may be necessary to introduce training to complement procedures stimulating axon regeneration.

Animals↗

Genetic parameters and trends for litter traits in U.S. Yorkshire, Duroc, Hampshire, and Landrace pigs.

Records on 251,296 Yorkshire, 75,262 Duroc, 83,338 Hampshire, and 53,234 Landrace litters born between 1984 and April of 1999 in herds on the National Swine Registry Swine Testing and Genetic Evaluation System were analyzed. Animal model and restricted maximum likelihood procedures were used to estimate variances of animal genetic (a), maternal genetic (m), permanent environmental, and service sire, and the covariances between a and m for number born alive (NBA), litter weight at 21 d (L21WT), and number weaned (NW). Fixed effects of contemporary groups were included in the analysis. Based on a single-trait model, estimates of heritabilities were 0.10, 0.09, 0.08, and 0.08 for NBA; 0.08, 0.07, 0.08, and 0.09 for L21WT; and 0.05, 0.07, 0.05, and 0.05 for NW in the Yorkshire, Duroc, Hampshire, and Landrace breeds, respectively. Estimates of maternal genetic effects were low and ranged from 0.00 to 0.02 for all traits and all breeds. Estimates of permanent environmental effects ranged from 0.03 to 0.08. Estimates of service sire effects ranged from 0.02 to 0.05. A bivariate analysis was used to estimate the genetic correlations among traits. Average genetic correlations over the four breeds were 0.13, 0.15, and 0.71 for NBA with L21WT, NBA with NW, and L21WT with NW, respectively. Average genetic trends were 0.018 pigs/yr, 0.114 kg/yr, and 0.004 pigs/yr for NBA, L21WT, and NW, respectively. Although estimates of heritabilities for litter traits were low and similar across breeds, genetic variances for litter traits were sufficiently large to indicate that litter traits could be improved through selection. This study presents the first set of breed-specific estimates of genetic parameters available from large numbers of field records. It provides information for use in national genetic evaluations.

Adipose Tissue↗

Evaluation of strategies for selection for lean growth rate in pigs.

Lean growth rate (LGR) in pigs is a nonlinear biological function of growth rate and lean quantity. According to animal breeding theory, genetic progress for LGR is maximized with selection on a linear index of its component traits, but selection on direct EBV for LGR is also common. In this study, the performance of five criteria for selection on estimated LGR in pigs was evaluated through simulation over five generations: linear indexes of multiple-trait EBV of component traits with or without updating index weights in each generation; a nonlinear index of multiple-trait EBV of component traits; and direct selection on EBV for LGR from a single-trait model or a multiple-trait model that included LGR and component traits. The nonlinear index yielded the highest response in LGR in Generation 5, but the linear index with updating performed almost as well. Not updating weights for the linear index reduced response in LGR by 1.1% in Generation 5 (P < 0.05). Direct selection on single-trait EBV for LGR yielded the lowest responses in Generation 5. Direct selection on EBV for LGR from a multiple-trait animal model yielded a 3.1% greater response in LGR in Generation 5 than direct selection on EBV for LGR based on a single-trait animal model (P < 0.05), but yielded a 1.9% lower response than the nonlinear index. Although differences in response in LGR were limited, alternative selection criteria resulted in substantially different responses in component traits. Linear index selection for LGR placed more emphasis on lean quantity, whereas direct selection for LGR emphasized growth rate. Based on the relative changes in the responses in LGR, selection for estimated LGR based on a nonlinear index or a linear index with updating is recommended for use in the swine industry.

Adipose Tissue↗

Genetic correlations between lean growth and litter traits in U.S. Yorkshire, Duroc, Hampshire, and Landrace pigs.

The objective of this study was to estimate breed-specific genetic correlations between lean growth and litter traits for four U.S. swine breeds. Records for lean growth and litter traits on Yorkshire, Duroc, Hampshire, and Landrace pigs collected between 1990 and April 2000 in herds on the National Swine Registry Swine Testing and Genetic Evaluation System were analyzed. A bivariate animal model and restricted maximum likelihood procedures were used to estimate genetic and environmental correlations between lean growth rate, days to 113.5 kg, backfat, and loin muscle area with litter traits of number born alive, litter weight at 21 d, and number weaned. Most genetic correlation estimates between lean growth and litter traits were small in magnitude and consistent across breeds. Backfat had the largest within-breed genetic correlations with number born alive (0.18 to 0.20) and litter weight at 21 d (-0.27 to -0.30). Estimates of genetic correlations between lean growth traits and number weaned were very small. Estimates of the environmental correlations between lean growth and litter traits also were very small for all traits and for all four breeds. Results indicate that selection for lean growth traits could have a long-term effect on litter traits. Including lean growth traits in a maternal-line evaluation using a multiple-trait model could increase the accuracy of the genetic evaluation for litter traits.

Adipose Tissue↗

Tamoxifen-induced endometrial cancer.

OBJECTIVE: Tamoxifen-induced endometrial changes in postmenopausal women with breast carcinoma are well-known. Due to the popularity of postoperative chemotherapy for breast cancer, chemotherapy-induced early menopause in women with breast cancer on tamoxifen treatment needs more attention, because these women have higher risk for endometrial cancers than premenopausal women. SUBJECT: From May 1995 to May 1997, three premenopausal women aged 46, 43, and 39 with breast cancer were treated in our center. All patients received standard surgery for their breast cancers followed by six courses of adjuvant chemotherapy and 5-year tamoxifen treatment. All patients were regularly followed-up at the Breast Cancer Center and evaluated annually at the gynecological clinics including pelvic examination, Pap smear and transvaginal sonography. RESULTS: All patients became menopausal after six courses of chemotherapy ranging from three months to 14 months. The endometrial cancers occurred at 36 months, 28 months, and 33 months, respectively, after initial treatment for the breast cancers. Their last gynecologic examinations performed at six months, eight months and five months before the diagnosis of endometrial cancer showed nothing remarkable. Only one patient complained of vaginal spotting before diagnosis and the other two patients only complained of increasing purulent vaginal discharge. All patients received standard treatment for endometrial cancer and none of them died of their disease but one patient died of recurrent breast cancer 52 months later. CONCLUSION: Women with breast cancer on tamoxifen treatment need more attention and frequent evaluation of their reproductive organs, especially postmenopausal (either spontaneous or chemotherapy induced) women, although the American College of Obstetricians and Gynecologists (ACOG) comments that no more than annual pelvic exams with Pap smears are needed in asymptomatic women.

Adult↗

Nutrient removal by the integrated use of high rate algal ponds and macrophyte systems in China.

High Rate Algal Ponds (HRAP) were operated at pilot scale to investigate the performance of HRAP under the temperate climate conditions of Shanghai, China. The results indicated that the HRAP gave good efficiency for nutrient removal, especially during summer. With a retention time of 4 or 8d according to the season, the annual average removal efficiencies for COD, NH4-N and PO4-P were 50%, 87% and 40%, respectively. The multi-factor linear models showed the relationships between nutrient removal efficiency and influencing factors. Using a macrophyte pond to separate algae from HRAP can achieve concentrations of COD, TP and TKN in the effluent at around 50 mg/L, 1.5 mg/L and 5 mg/L respectively.

Biodegradation, Environmental↗