Biomedical subjects

Lijun Ma

Publications and source records attributed to Lijun Ma.

At least 19 recordsLinked to original sources

PubMed2006

Physiological evidence for the involvement of peptide YY in the regulation of energy homeostasis in humans.

OBJECTIVE: To explore the potential role of the endogenous peptide YY (PYY) in the long-term regulation of body weight and energy homeostasis. RESEARCH METHODS AND PROCEDURES: Fasting and postprandial plasma PYY concentrations were measured after an overnight fast and 30 to 180 minutes after a standardized meal in 29 (21 men/8 women) non-diabetic subjects, 16 of whom had a follow-up visit 10.8 +/- 1.4 months later. Ratings of hunger and satiety were collected using visual analog scales. Resting metabolic rate (RMR) (15-hour RMR) and respiratory quotient (RQ) were assessed using a respiratory chamber. RESULTS: Fasting PYY concentrations were negatively correlated with various markers of adiposity and negatively associated with 15-hour RMR (r = -0.46, p = 0.01). Postprandial changes in PYY (area under the curve) were positively associated with postprandial changes in ratings of satiety (r = 0.47, p = 0.01). The maximal PYY concentrations achieved after the meal (peak PYY) were negatively associated with 24-hour RQ (r = -0.41, p = 0.03). Prospectively, the peak PYY concentrations were negatively associated with changes in body weight (r = -0.58, p = 0.01). DISCUSSION: Our data indicate that the endogenous PYY may be involved in the long-term regulation of body weight. It seems that this long-term effect was not exclusively driven by the modulation of food intake but also by the control of energy expenditure and lipid metabolism.

Adolescent↗

PubMed2006

CHRM3 gene variation is associated with decreased acute insulin secretion and increased risk for early-onset type 2 diabetes in Pima Indians.

The muscarinic acetylcholine receptor subtype M3 (CHRM3) gene is expressed in islet beta-cells and has a role in stimulating insulin secretion; therefore, CHRM3 was analyzed as a candidate gene for type 2 diabetes in Pima Indians. Ten variants were genotyped in a family-based sample (n = 1,037), and 1 variant (rs3738435) located in the 5' untranslated region of an alternative transcript was found to be modestly associated with both early-onset type 2 diabetes and the acute insulin response in a small subset of these subjects. To better assess whether this variant has a role in acute insulin secretion, which could affect risk for early-onset type 2 diabetes, rs3738435 was genotyped in a larger group of normal glucose-tolerant Pima Indians who had measures of acute insulin secretion (n = 282) and a larger case-control group of Pima Indians selected for early-onset type 2 diabetes (n = 348 case subjects with age of onset <25 years; n = 392 nondiabetic control subjects aged >45 years). Genotyping in these larger sets of subjects confirmed that the C allele of rs3738435 was associated with a reduced acute insulin response (adjusted P = 0.00006) and was also modestly associated with increased risk of early-onset type 2 diabetes (adjusted P = 0.02).

Adipose Tissue↗

PubMed2005

Simultaneous integrated intensity-modulated radiotherapy boost for locally advanced gynecological cancer: radiobiological and dosimetric considerations.

PURPOSE: Whole-pelvis irradiation (WPI) followed by a boost to the tumor site is the standard of practice for the radiotherapeutic management of locally advanced gynecologic cancers. The boost is frequently administered by use of brachytherapy or, occasionally, external-beam radiotherapy (EBRT) when brachytherapy does not provide sufficient coverage because of the size of the tumor or the geometry of the patient. In this work, we propose using an intensity-modulated radiotherapy (IMRT) simultaneous integrated boost (SIB), which is a single-phase process, to replace the conventional two-phase process involving WPI plus a boost. Radiobiological modeling is used to design appropriate regimens for the IMRT SIB. To demonstrate feasibility, a dosimetric study is carried out on an example patient. METHODS AND MATERIALS: The standard linear-quadratic (LQ) model is used to calculate the biologically effective dose (BED) and equivalent uniform dose (EUD). A series of regimens that are biologically equivalent to those conventional two-phase treatments is calculated for the proposed SIB. A commercial inverse planning system (Corvus) was used to generate IMRT SIB plans for a sample patient case that used the newly designed fractionations. The dose-volume histogram (DVH) and EUD of both the target and normal structures for conventional treatments and the SIB are compared. A sparing factor was introduced to characterize the sparing of normal structures. RESULTS: Fractionation regimes that are equivalent to the conventional treatments and are suitable for the IMRT SIB are deduced. For example, a SIB plan with 25 x 3.1 Gy (77.5 Gy) to a tumor is equivalent to a conventional treatment of EBRT of 45 Gy to the whole pelvis in 25 fractions plus a high-dose rate (HDR) brachytherapy boost with 30 Gy in 5 fractions. The normal tissue BED is found to be lower for the SIB plan than for the whole-pelvis plus HDR scheme when a sparing factor for the critical structures is considered. This finding suggests that the IMRT SIB has a better therapeutic ratio. Three IMRT SIB plans with 25 x 1.8 Gy to the pelvic nodes and 25 x 2.4 Gy (60 Gy), 25 x 2.8 Gy (70 Gy), and 25 x 3.2 Gy (80 Gy) to the tumor site were generated for the example patient case. The target coverage ranged from 94% to 95.5%. The sparing of bladder and rectum is significantly improved with the 60 to 70 Gy SIB treatments, as compared with the conventional treatments. The proposed SIB treatment can reduce the treatment time to 5 weeks. CONCLUSIONS: An IMRT simultaneous integrated boost to replace the conventional two-phase treatments (whole pelvic irradiation followed by brachytherapy or EBRT boost) is radiobiologically and dosimetricaly feasible for locally advanced gynecological cancers that may not be amenable to brachytherapy for anatomic or medical reasons. In addition to its shorter treatment time, the proposed IMRT SIB can provide significant sparing to normal structures, which offers potential for dose escalation. Issues such as organ motion and changing anatomy as tumor responds still must be addressed.

Female↗

PubMed2005

A constrained tracking algorithm to optimize plug patterns in multiple isocenter gamma knife radiosurgery planning.

We developed a source blocking optimization algorithm for Gamma Knife radiosurgery, which is based on tracking individual source contributions to arbitrarily shaped target and critical structure volumes. A scalar objective function and a direct search algorithm were used to produce near real-time calculation results. The algorithm allows the user to set and vary the total number of plugs for each shot to limit the total beam-on time. We implemented and tested the algorithm for several multiple-isocenter Gamma Knife cases. It was found that the use of limited number of plugs significantly lowered the integral dose to the critical structures such as an optical chiasm in pituitary adenoma cases. The main effect of the source blocking is the faster dose falloff in the junction area between the target and the critical structure. In summary, we demonstrated a useful source-plugging algorithm for improving complex multi-isocenter Gamma Knife treatment planning cases.

Algorithms↗

PubMed2005

Concomitant GRID boost for Gamma Knife radiosurgery.

We developed an integrated GRID boost technique for Gamma Knife radiosurgery. The technique generates an array of high dose spots within the target volume via a grid of 4-mm shots. These high dose areas were placed over a conventional Gamma Knife plan where a peripheral dose covers the full target volume. The beam weights of the 4-mm shots were optimized iteratively to maximize the integral dose inside the target volume. To investigate the target volume coverage and the dose to the adjacent normal brain tissue for the technique, we compared the GRID boosted treatment plans with conventional Gamma Knife treatment plans using physical and biological indices such as dose-volume histogram (DVH), DVH-derived indices, equivalent uniform dose (EUD), tumor control probabilities (TCP), and normal tissue complication probabilities (NTCP). We found significant increase in the target volume indices such as mean dose (5%-34%; average 14%), TCP (4%-45%; average 21%), and EUD (2%-22%; average 11%) for the GRID boost technique. No significant change in the peripheral dose coverage for the target volume was found per RTOG protocol. In addition, the EUD and the NTCP for the normal brain adjacent to the target (i.e., the near region) were decreased for the GRID boost technique. In conclusion, we demonstrated a new technique for Gamma Knife radiosurgery that can escalate the dose to the target while sparing the adjacent normal brain tissue.

Algorithms↗

PubMed2005

Variations in peptide YY and Y2 receptor genes are associated with severe obesity in Pima Indian men.

Peptide YY (PYY) and Y2 receptor (Y2R) may be important in the central regulation of body weight and food intake. To determine whether genetic variation in PYY and/or Y2R may contribute to morbid obesity in humans, these genes were sequenced in 83 extremely obese Pima Indians (BMI > or = 50 kg/m2). Sequencing of PYY identified three single nucleotide polymorphisms (SNPs) in the untranslated region. Sequencing of the Y2R coding region identified one missense (Ala172Thr) substitution and two silent substitutions. Eight additional SNPs in the 5' untranslated region of Y2R were identified from public databases. These SNPs were genotyped in 489 full-heritage adult Pimas (362 severely obese and 127 nondiabetic, nonobese subjects), who are not first-degree relatives, for association analysis. The PYY variants were not associated with obesity, whereas four variants from two haplotype blocks in Y2R were marginally associated (P = 0.054-0.067) with obesity. However, if the analysis was restricted to men (n = 167, 100 obese and 67 lean), the PYY variants and two SNPs in Y2R that were in complete linkage disequilibrium were significantly associated with severe obesity (P = 0.001 and P = 0.002, respectively). Our data suggest that the PYY-Y2R pathway may influence body weight through a sex-specific mechanism, but this finding requires confirmation in other populations.

5' Untranslated Regions↗

PubMed2004

Structural and orientational studies of chiral N-[4(1-pyrene)butyroyl]-phenylalanine in cast film.

Cast films of chiral material N-[4(1-pyrene)butyroyl]-l-phenylalanine (Py-l-Phe) and the racemic modification (the 1:1 mixture of Py-l-Phe and Py-d-Phe) have been investigated in the present study. The microscopic structure, molecular orientation and the aggregation in the film have been studied by using ultraviolet-visible (UV-vis) and infrared (IR) spectroscopy. When a cast film is formed from the chloroform solution at room temperature, the J-aggregates of Py-l-Phe and Py-d-Phe are observed by UV-vis spectra. A comparison of Fourier transform infrared (FT-IR) transmission and reflection-absorption (RA) spectroscopy has been applied to reveal the orientation and structural characterization of the cast films. It has been found that the pyrenyl ring in the cast film of Py-l-Phe assumes a nearly vertical orientation with respect to the surface of the solid substrate. And there are two different hydrogen bonding species, cyclic dimer and linear dimer, exist in carboxyl groups in cast films. The detailed analysis of the OH and NH stretching modes of Py-l-Phe and Py-d-Phe allows us to reveal the hydrogen bonds existing in the films.

Chloroform↗

PubMed2004

Selective source blocking for Gamma Knife radiosurgery of trigeminal neuralgia based on analytical dose modelling.

We have developed an automatic critical region shielding (ACRS) algorithm for Gamma Knife radiosurgery of trigeminal neuralgia. The algorithm selectively blocks 201 Gamma Knife sources to minimize the dose to the brainstem while irradiating the root entry area of the trigeminal nerve with 70-90 Gy. An independent dose model was developed to implement the algorithm. The accuracy of the dose model was tested and validated via comparison with the Leksell GammaPlan (LGP) calculations. Agreements of 3% or 3 mm in isodose distributions were found for both single-shot and multiple-shot treatment plans. After the optimized blocking patterns are obtained via the independent dose model, they are imported into the LGP for final dose calculations and treatment planning analyses. We found that the use of a moderate number of source plugs (30-50 plugs) significantly lowered (approximately 40%) the dose to the brainstem for trigeminal neuralgia treatments. Considering the small effort involved in using these plugs, we recommend source blocking for all trigeminal neuralgia treatments with Gamma Knife radiosurgery.

Algorithms↗

PubMed2004

Improving a scissor-action couch for conformal arc radiotherapy and radiosurgery.

We have developed a method to improve the setup accuracy of a Varian Clinac 6/100 couch for delivering conformal arc therapy using a tertiary micro multileaf collimator (MLC) system. Several immobilization devices have been developed to improve the mechanical stability and isocenter alignment of the couch: turn-knob harnesses, double-track alignment plates, and a drop-in rod that attaches the couch to the concrete floor. These add-on components minimize the intercomponent motion of the couch's scissor elevator, which allows consistent treatment setup. The accuracy of our isocenter couch alignment is an improvement over the above devices, within 1 mm of their accuracy. The couch has been used with over 15 patients and with over 50 modulated conformal arc treatment deliveries at our institution.

Artifacts↗

PubMed2004

Magnetic collimation and metal foil filtering for electron range and fluence modulation.

We investigated the use of magnetically collimated electron beams together with metal filters for electron fluence and range modulation. A longitudinal magnetic field collimation method was developed to reduce skin dose and to improve the electron beam penumbra. Thin metal foils were used to adjust the energies of magnetically collimated electrons. The effects for different types of foils such as Al, Be, Cu, Pb, and Ti were studied using Monte Carlo calculations. An empirical pencil beam dose calculation model was developed to calculate electron dose distributions under magnetic collimation and foil modulation. An optimization method was developed to produce conformal dose distributions for simulated targets such as a horseshoe-shaped target. Our results show that it is possible to produce an electron depth dose enhancement peak using similar techniques of producing a spread-out Bragg peak. In conclusion, our study demonstrates new aspects of using magnetic collimation and foil filtration for producing fluence and range modulated electron dose distributions.

Algorithms↗

PubMed2004

Simultaneous minimizing monitor units and number of segments without leaf end abutment for segmental intensity modulated radiation therapy delivery.

Leaf end abutment is seldom studied when delivering segmental intensity modulated radiation therapy (IMRT) fields. We developed an efficient leaf sequencing method to eliminate leaf end abutment for segmental IMRT delivery. Our method uses simple matrix and sorting operations to obtain a solution that simultaneously minimizes total monitor units and number of segments without leaf end abutment between segments. We implemented and demonstrated our method for multiple clinical cases. We compared the results of our method with the results from exhaustive search method. We found that our solution without leaf end abutment produced equivalent results to the unconstrained solutions in terms of minimum total monitor units and minimum number of leaf segments. We conclude that the leaf end abutment fields can be avoided without affecting the efficiency of segmental IMRT delivery. The major strength of our method is its simplicity and high computing speed. This potentially provides a useful means for generating segmental IMRT fields that require high spatial resolution or complex intensity distributions.

Algorithms↗

PubMed2004

Dosimetric properties of magnetically collimated electron beams for radiation therapy.

A method of generating magnetically collimated electron beams is developed and the dosimetric properties of magnetically collimated electrons are investigated. An in-air magnetic collimator device was designed and constructed for the study. The magnetic collimator was placed above the exit port of a 14 x 14 cm2 electron cone. Axial magnetic field of approximately 0.6 Tesla is generated inside the collimator via an array of permanent magnets. Fixed and rotational magnetically collimated electron beams were delivered and measured in phantoms. We found that magnetically collimated electron beams significantly lower the surface dose as compared with conventional electron beams. A magnetically collimated arc beam further reduces the surface dose to less than 20% of the maximum dose inside the target. The dose per monitor unit at d(max) for the magnetically collimated electron beams was significantly (approximately 40%) higher than that of the conventional electron beams. The use of magnetic collimation may lead to improved delivery techniques for breast and head and neck cancer treatments.

Electrons↗

PubMed2004

Melanocortin 4 receptor gene variation is associated with severe obesity in Pima Indians.

Heterozygous coding mutations in the melanocortin 4 receptor gene (MC4R) are the most common genetic causes of severe human obesity identified to date. To determine whether MC4R has a role in causing severe obesity in Pima Indians, we sequenced the coding region of this gene in 426 full-heritage, non-first-degree related, adult Pima Indians (300 severely obese and 126 nondiabetic nonobese control subjects). Three coding variations were detected as heterozygotes only in severely obese subjects. One variation, detected in three obese subjects, was a novel single-base insertion (A) at nucleotide 100, and it predicted a frameshift and premature STOP at codon 37. The second variant, detected in 10 obese subjects, predicted a previously identified arginine-to-glutamine substitution at codon 165, and the third variant, detected in one obese subject, predicted a novel glycine-to-serine substitution at codon 231. Three polymorphisms were also identified in the 5' untranslated region, but these variants were detected in both obese and lean subjects and had similar allele frequencies. We conclude that variations in MC4R may account for a small portion of obesity in Pima Indians, but they do not explain the overall high prevalence of obesity in this Native American population.

Adult↗

PubMed2003

A technique to sharpen the beam penumbra for Gamma Knife radiosurgery.

In stereotactic radiosurgery, a narrow beam penumbra is often desired for producing steep dose fall-off between the target volume and adjacent critical structures. Due to limited source sizes and the scattering effects, the physical penumbra of the Gamma Knife (GK) is often restricted to a width of 1-2 mm. In this work, we developed a technique to further reduce the beam penumbra and improve the dose profile for the Gamma Knife delivery. Under this technique, a conic filter is inserted into an individual plug collimator of a GK helmet to flatten the beam profile. Monte Carlo calculations were carried out to simulate the GK geometry of the individual plug collimator and to optimize the physical shapes of the filters. The calculations were performed for a series of filter shapes with different collimator sizes. Our results show that a proper filter significantly reduces the single GK beam penumbra width (defined as the distance from the 90% to 50% isodose lines) by 30-60%. The beam intensity is reduced by about 20-50% when the filter is used. A treatment plan was developed for a trigeminal neuralgia case by commissioning the filtered beam profile for Leksell Gamma Plan (version 5.31). Compared with the conventional treatment plan, a significant improvement was found on the critical structure sparing and on the target dose uniformity. In conclusion, the proposed technique is feasible and effective in sharpening the beam penumbra for Gamma Knife beam profiles.

Algorithms↗

PubMed2003

Concomitant boost of stratified target area with gamma knife radiosurgery: a treatment planning study.

Conventional Gamma Knife Stereotactic Radiosurgery (GKSRS) has been focused on delivering a single peripheral dose to the gross target volume based on the anatomic information derived from the magnetic resonance or computed tomography (CT) studies. In this study, we developed a treatment planning approach that allows a boost dose to be delivered concomitantly to the desired subtarget area while maintaining the peripheral isodose coverage of the target volume. The subtarget area is defined as the high-risk or the tumor burden areas based on the functional imaging information such as the magnetic resonance spectroscopy (MRS) studies or the physician's clinical diagnosis. Treatment plan comparisons were carried out between the concomitant boost plans and the conventional treatment plans using dose volume histogram (DVH), tissue volume ratio (TVR), and the maximum dose to the peripheral dose ratio (MD/PD) analysis. Using the concomitant boost approach, more conformal and higher dose was delivered to the desired subtarget area while maintaining the peripheral isodose coverage of the gross target volume (GTV). Additionally, the dose to the normal brain tissue was found to be equivalent between the concomitant boost plans and the conventional plans. As a result, we conclude that concomitant boost of a stratified target area is feasible for GKSRS.

Brain Neoplasms↗

PubMed2003

A quality assurance method for analyzing and verifying intensity modulated fields.

A quality assurance method is developed for measuring, verifying and analyzing intensity modulated radiation fields. It is applicable for rotational and fixed-beam intensity modulated radiation therapy (IMRT) treatments. A gantry-mount device was constructed to measure the transmission dose of an IMRT field using radiographic films. A double-exposure technique with optimal kernel estimate method was developed to minimize the errors from measurements. A chi2 confidence level test method was developed to detect the discrepancies between measured and prescribed IMRT fluence distributions. Our method was tested for rotational and fixed-beam IMRT treatment verifications. The method was found insensitive to the hardware-related parameters for rotational and fixed-beam IMRT deliveries. The chi2 confidence level test was found to be more sensitive than linear correlation method in detecting relative small errors for cases with a few segments or narrow regions of interest. In conclusion, we demonstrated a quantitative method for verifying and analyzing IMRT treatment deliveries.

Models, Statistical↗

PubMed2003

Linkage analysis of five Chinese families with arrhythmogenic right ventricular cardiomyopathy using microsatellite genetic markers.

OBJECTIVE: To explore the linkage relationship between specific genetic markers and arrhythmogenic right ventricular cardiomyopathy (ARVC) in Chinese pedigrees. METHODS: The microsatellite genetic markers D2S152, D14S252, and D10S1664 were studied for their linkages to ARVC in five Chinese ARVC pedigrees and a normal population of 121 Chinese individuals. Genomic DNA of the pedigrees and normal population was amplified using PCR techniques. Denaturing polyacrylamide sequencing gel (4%) electrophoresis was used to detect microsatellite repeat polymorphisms. Gels were silver-stained. A classical linkage analysis program was used assuming models of autosomal dominance and recession. RESULTS: The logarithm of the odds (LOD) scores of D2S152 with ARVC in LW, WD, DS, LC and TY pedigrees were 2.174, -0.589, -infinity, - (indicating that linkage is not supported in this mode), and -infinity respectively in autosomal dominant model (recombination fraction = 0.000 respectively)and were -infinity, -infinity, -infinity, -infinity, and 0.182 respectively in the autosomal recessive model. The LOD scores of D14S252 with ARVC in LW, WD, DS, LC and TY pedigrees were -, -, -infinity, -, and 0 respectively in autosomal dominant model, and were -infinity, -0.812, -infinity, -infinity, and 0.087 respectively in autosomal recessive model. The LOD scores of D2S152 with ARVC in LW, WD, DS, LC and TY pedigrees were -, -0.539, -, and 0.602 respectively in autosomal dominant model and were -, -infinity, -infinity, -infinity, and - infinity respectively in autosomal recessive model. CONCLUSIONS: The LOD score for D2S152 in the LW pedigree was 2.174, indicating that the chance of linkage is about 150:1. This suggests that there is a possible ARVC-related gene near this marker. There were no clear linkage relationships between ARVC and D10S1664 and D14S252 in this family, and no linkages between ARVC and any of the three genetic markers in the other four families. These results also suggest that there is genetic heterogeneity in LW and in the other pedigrees.

Arrhythmogenic Right Ventricular Dysplasia↗

PubMed2002

Clinical implementation of intensity-modulated arc therapy.

PURPOSE: Intensity-modulated arc therapy (IMAT) is a method for delivering intensity-modulated radiation therapy (IMRT) using rotational beams. During delivery, the field shape, formed by a multileaf collimator (MLC), changes constantly. The objectives of this study were to (1) clinically implement the IMAT technique, and (2) evaluate the dosimetry in comparison with conventional three-dimensional (3D) conformal techniques. METHODS AND MATERIALS: Forward planning with a commercial system (RenderPlan 3D, Precision Therapy International, Inc., Norcross, GA) was used for IMAT planning. Arcs were approximated as multiple shaped fields spaced every 5-10 degrees around the patient. The number and ranges of the arcs were chosen manually. Multiple coplanar, superimposing arcs or noncoplanar arcs with or without a wedge were allowed. For comparison, conventional 3D conformal treatment plans were generated with the same commercial forward planning system as for IMAT. Intensity-modulated treatment plans were also created with a commercial inverse planning system (CORVUS, Nomos Corporation). A leaf-sequencing program was developed to generate the dynamic MLC prescriptions. IMAT treatment delivery was accomplished by programming the linear accelerator (linac) to deliver an arc and the MLC to step through a sequence of fields. Both gantry rotation and leaf motion were enslaved to the delivered MUs. Dosimetric accuracy of the entire process was verified with phantoms before IMAT was used clinically. For each IMAT treatment, a dry run was performed to assess the geometric and dosimetric accuracy. Both the central axis dose and dose distributions were measured and compared with predictions by the planning system. RESULTS: By the end of May 2001, 50 patients had completed their treatments with the IMAT technique. Two to five arcs were needed to achieve highly conformal dose distributions. The IMAT plans provided better dose uniformity in the target and lower doses to normal structures than 3D conformal plans. The results varied when the comparison was made with fixed gantry IMRT. In general, IMAT plans provided more uniform dose distributions in the target, whereas the inverse-planned fixed gantry treatments had greater flexibility in controlling dose to the critical structures. Because the field sizes and shapes used in the IMAT were similar to those used in conventional treatments, the dosimetric uncertainty was very small. Of the first 32 patients treated, the average difference between the measured and predicted doses was -0.54 +/- 1.72% at isocenter. The 80%-95% isodose contours measured with film dosimetry matched those predicted by the planning system to within 2 mm. The planning time for IMAT was slightly longer than for generating conventional 3D conformal plans. However, because of the need to create phantom plans for the dry run, the overall planning time was doubled. The average time a patient spent on the table for IMAT treatment was similar to conventional treatments. CONCLUSION: Initial results demonstrated the feasibility and accuracy of IMAT for achieving highly conformal dose distributions for different sites. If treatment plans can be optimized for IMAT cone beam delivery, we expect IMAT to achieve dose distributions that rival both slice-based and fixed-field IMRT techniques. The efficient delivery with existing linac and MLC makes IMAT a practical choice.

Brain Neoplasms↗