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Biomedical subjects

L Ma

Publications and source records attributed to L Ma.

At least 163 records · Page 9Linked to original sources
PubMed2000

Fatigue behavior of a pyrolytic carbon.

The test method introduced here enables the fatigue test of a brittle material at a stress level that is as high as its ultimate fracture strength. The procedural design of the test eliminates uncertainties that often make interpretation of the results difficult. The results, using a statistical analysis, demonstrate that isotropic pyrolytic carbons are fatigue-free in physiologically relevant stress regimes encountered in contemporary bi-leaflet artificial heart-valve designs. Verification tests show that the material can withstand cyclic stress of 10(9) cycles at a strain level that equals that of the mean static strength.

Algorithms↗
PubMed2000

Prenatal diagnosis of fetal heart failure in twin reversed arterial perfusion syndrome.

Diagnosis of twin reversed arterial perfusion (TRAP) syndrome is a rare fetal anomaly that can be misdiagnosed on prenatal ultrasound. We confirmed the use of colour-flow Doppler for prenatal diagnosis of TRAP syndrome and used serial fetal echocardiography for non-invasive evaluation of the fetus. A patient with twin intrauterine pregnancy was referred to our centre with suspected intrauterine fetal demise following a 16 week ultrasound. Serial colour-flow Doppler ultrasonography demonstrated retrograde arterial flow in an acardiac twin. Following diagnosis of TRAP syndrome, serial fetal echocardiography was employed to follow the normal twin for signs of heart failure, including right atrial dilation, tricuspid regurgitation and pericardial effusion. When early signs of fetal heart failure were suspected a viable female infant was delivered at 32 weeks' gestation. We suggest that serial fetal echocardiography represents a non-invasive approach that can be used to follow fetal cardiac function of the normal twin in TRAP syndrome.

Adult↗
PubMed2000

Dosimetric effects of patient displacement and collimator and gantry angle misalignment on intensity modulated radiation therapy.

PURPOSE AND OBJECTIVE: The primary goal of this study was to examine systematically the dosimetric effect of small patient movements and linear accelerator angular setting misalignments in the delivery of intensity modulated radiation therapy. We will also provide a method for estimating dosimetric errors for an arbitrary combination of these uncertainties. MATERIALS AND METHODS: Sites in two patients (lumbar-vertebra and nasopharynx) were studied. Optimized intensity modulated radiation therapy treatment plans were computed for each patient using a commercially available inverse planning system (CORVUS, NOMOS Corporation, Sewickley, PA). The plans used nine coplanar beams. For each patient the dose distributions and relevant dosimetric quantities were calculated, including the maximum, minimum, and average doses in targets and sensitive structures. The corresponding dose volumetric information was recalculated by purposely varying the collimator angle or gantry angle of an incident beam while keeping other beams unchanged. Similar calculations were carried out by varying the couch indices in either horizontal or vertical directions. The intensity maps of all the beams were kept the same as those in the optimized plan. The change of a dosimetric quantity, Q, for a combination of collimator and gantry angle misalignments and patient displacements was estimated using Delta=Sigma(DeltaQ/Deltax(i))Deltax(i). Here DeltaQ is the variation of Q due to Deltax(i), which is the change of the i-th variable (collimator angle, gantry angle, or couch indices), and DeltaQ/Deltax(i) is a quantity equivalent to the partial derivative of the dosimetric quantity Q with respect to x(i). RESULTS: While the change in dosimetric quantities was case dependent, it was found that the results were much more sensitive to small changes in the couch indices than to changes in the accelerator angular setting. For instance, in the first example in the paper, a 3-mm movement of the couch in the anterior-posterior direction can cause a 38% decrease in the minimum target dose or a 41% increase in the maximum cord dose, whereas a 5 degrees change in the θ(1)=20 degrees beam only gave rise to a 1.5% decrease in the target minimum or 5.1% in the cord maximum. The effect of systematic positioning uncertainties of the machine settings was more serious than random uncertainties, which tended to smear out the errors in dose distributions. CONCLUSIONS: The dose distribution of an intensity modulated radiation therapy (IMRT) plan changes with patient displacement and angular misalignment in a complex way. A method was proposed to estimate dosimetric errors for an arbitrary combination of uncertainties in these quantities. While it is important to eliminate the angular misalignment, it was found that the couch indices (or patient positioning) played a much more important role. Accurate patient set-up and patient immobilization is crucial in order to take advantage fully of the technological advances of IMRT. In practice, a sensitivity check should be useful to foresee potential IMRT treatment complications and a warning should be given if the sensitivity exceeds an empirical value. Quality assurance action levels for a given plan can be established out of the sensitivity calculation.

Humans↗
PubMed2000

A study on producing monoclonal antibody with one diagnostic marker screened electrophoretically from the urine of individuals infected with Schistosoma japonicum.

One diagnostic marker (a glycoprotein with 30kDa) from the urine of individuals infected with S. japonicum was screened with electrophoresis, and used as antigen to produce McAbs. Two lines of McAbs, named NP56 and NP54,were obtained. McAb NP56 was of better immunoreactivity and its immunoglobulin isotype was IgG(2b.) McAb NP56 could react with SEA (soluble egg antigen) and AWA (adult worm antigen) and express on miracidia in eggs of S. japonicum. When determined with NP56 as a probe in indirect ELISA, the sensitivity and specificity of positive urine samples (EPG median 69) was 50% and 80% in original urine samples, and 90% and 100% in concentrated urine samples, respectively. The results above indicated that with established means it is feasible to produce McAb with the diagnostic marker screened electrophoretically from the metabolic product of the individuals infected with this pathogen, and that McAb-NP56 is of potential value in the diagnosis of chronic cases and individuals with light infection with S. japonicum.

Animals↗
PubMed2000

The 'ins' and 'outs' of intermediate filament organization.

A major function shared by several types of cytoplasmic intermediate filaments (IFs) is to stabilize cellular architecture against the mechanical forces it is subjected to. As for other fibrous cytoskeletal arrays, a crucial determinant of this function is the spatial organization of IFs in the cytoplasm. However, very few crossbridging proteins are specific for IFs - most IF-associated proteins known to exert a structural role act to tether IFs to other major cytoskeletal elements, such as F-actin, microtubules or adhesion complexes. In addition, IFs are endowed with the ability to participate in their own organization. This intriguing property is probably connected to the unusual degree of sequence diversity and sequence-specific regulation that characterize IF genes and their proteins. This dependence upon a combination of extrinsic and intrinsic determinants contributes to distinguish IFs from other fibrous cytoskeletal polymers and is key to their function.

Eukaryotic Cells↗
PubMed2000

Anti-galactose-alpha(1,3) galactose antibody production in alpha1,3-galactosyltransferase gene knockout mice after xeno and allo transplantation.

Antibodies (Abs) that mediate the hyperacute rejection and acute vascular rejection/delayed xenograft rejection of pig organs in humans and Old World primates are predominantly directed at a single carbohydrate epitope, galactose-alpha1,3-galactose (alpha1,3Gal). The T-cell dependence of elicited anti-alpha1,3Gal Ab responses in humans and Old World primates is controversial. In this study we have characterized anti-alpha1,3Gal Ab production in mice with disrupted alpha1,3-galactosyltransferase genes (GT-Ko mice) and determined the T-cell dependence of anti-alpha1,3Gal Ab responses, following xenograft and allograft transplantation. GT-Ko mice produce natural anti-alpha1,3Gal IgM and IgG in an age-dependent manner, however, these Abs could not elicit hyperacute rejection nor affect the rate of cardiac xenograft (3-5 days) or allograft rejection (7-9 days). Transplantation of xenogeneic Lewis rats hearts elicited modest anti-alpha1,3Gal Ab, but vigorous xenoAb responses. The anti-alpha1,3Gal Ab response was restricted to the IgM and IgG3 subclass while the xenoAb response comprised IgM and all four IgG subclasses. Transplantation of allogeneic C3H hearts elicited weak anti-alpha1,3Gal Ab responses that were primarily IgM, but vigorous alloAb responses. Despite the restriction of elicited anti-alpha 1,3Gal Ab responses to the IgM and IgG3 isotypes, these responses are T-cell dependent. The ability of allografts to elicit weak anti-alpha1,3Gal but strong allo-Ab responses, can be explained by the dependence of alpha1,3Gal-specific B cells on cognate help from T cells.

Age Factors↗
PubMed2000

Role of anger in antral motor activity in irritable bowel syndrome.

There is considerable evidence indicating that patients with irritable bowel syndrome respond to emotional and environmental stimulation with increased colon motor activity. It has been suggested also that increased colon motor activity is not confined to the colon and may be representative of a broader disorder affecting the rest of the gastrointestinal tract in this population. The results of our current study suggest that anger may have a significant, although differential effect on antral motor activity in IBS patients compared to normal controls. We found that while antral motor activity did not differ significantly in our groups during rest, anger decreased antral motor activity in IBS patients and increased antral motor activity in normal controls. The difference was not attributable to a difference in anger levels since the groups did not differ in their response to the standardized anger stressor. Rather, the difference in the antral motor response appears to be qualitative and a possible marker for irritable bowel syndrome. Our data further suggest that increased colon motor activity in IBS patients during emotional stress is not a result of a rise in motor activity throughout the gastrointestinal tract, but a phenomenon that may be unique to the colon in this patient population.

Adult↗
PubMed2000

Non-depleting anti-CD4, but not anti-CD8, antibody induces long-term survival of xenogeneic and allogeneic hearts in alpha1,3-galactosyltransferase knockout (GT-Ko) mice.

The anti-galactose-alpha1,3-galactose (Gal) antibody (Ab) response following pig-to-human transplantation is vigorous and largely resistant to currently available immunosuppression. The recent generation of GT-Ko mice provides a unique opportunity to study the immunological basis of xenograft-elicited anti-Gal Ab response in vivo, and to test the efficacy of various strategies at controlling this Ab response [1]. In this study, we compared the ability of non-depleting anti-CD4 and anti-CD8 to control rejection and antibody production in GT-Ko mice following xenograft and allograft transplantation. Hearts from baby Lewis rat or C3H mice were transplanted heterotopically into GT-Ko. Non-depleting anti-CD4 (YTS177) and anti-CD8 (YTS105) Abs were used at 1 mg/mouse, and given as four doses daily from day -2 to 1 then q.o.d. till day 21. Xenograft rejection occurred at 3 to 5 days post-transplantation in untreated GT-Ko recipients, and was histologically characterized as vascular rejection. Anti-CD4, but not anti-CD8, Ab treatment prolonged xenograft survival to 68 to 74 days and inhibited anti-Gal Ab as well as xeno-Ab production. In four of the five hearts from anti-CD4 mAbs-treated GT-Ko mice, we observed classic signs of chronic rejection, namely, thickened intima in the lumen of vessels, significant IgM deposition, fibrosis and modest mononuclear cell infiltrate of Mac-1+ macrophages and scattered T cells (CD8>CD4). Xenograft rejection in untreated, as well as anti-CD4- and anti-CD8-treated, recipients was associated with increased intragraft IL-6, IFN-gamma and IL-10 mRNA. C3H allografts were rejected in 7 to 9 days by untreated GT-Ko mice and were histologically characterized as cellular rejection. Treatment with anti-CD4 and anti-CD8 mAb resulted in graft survivals of >94.8 and 11.8 days, respectively. Anti-CD4 mAb treatment resulted in a transient inhibition of alloreactive and anti-Gal Ab production. The presence of circulating alloreactive and anti-Gal Abs at >50 days post-transplant was associated with significant IgM and IgG deposition in the graft. Yet, in the anti-CD4 mAb-treated group, the allografts showed no signs of rejection at the time of sacrifice (>100 days post-transplantation). All rejected allografts had elevated levels of intragraft IL-6, IFN-gamma and IL-10 mRNA, while the long-surviving anti-CD4-treated allografts had reduced mRNA levels of these cytokines. Collectively, our studies suggest that the elicited xeno-antibody production and anti-Gal Ab production in GT-Ko mice are CD4+ T-cell dependent. The majority of xenografts succumbed to chronic rejection, while allografts survived with minimal histological change, despite elevated levels of circulating alloAbs. Thus, immunosuppression with anti-CD4 mAb therapy induces long-term survival of allografts more effectively than to xenografts.

Animals↗
PubMed2000

Msx2 deficiency in mice causes pleiotropic defects in bone growth and ectodermal organ formation.

The composite structure of the mammalian skull, which forms predominantly via intramembranous ossification, requires precise pre- and post-natal growth regulation of individual calvarial elements. Disturbances of this process frequently cause severe clinical manifestations in humans. Enhanced DNA binding by a mutant MSX2 homeodomain results in a gain of function and produces craniosynostosis in humans. Here we show that Msx2-deficient mice have defects of skull ossification and persistent calvarial foramen. This phenotype results from defective proliferation of osteoprogenitors at the osteogenic front during calvarial morphogenesis, and closely resembles that associated with human MSX2 haploinsufficiency in parietal foramina (PFM). Msx2-/- mice also have defects in endochondral bone formation. In the axial and appendicular skeleton, post-natal deficits in Pth/Pthrp receptor (Pthr) signalling and in expression of marker genes for bone differentiation indicate that Msx2 is required for both chondrogenesis and osteogenesis. Consistent with phenotypes associated with PFM, Msx2-mutant mice also display defective tooth, hair follicle and mammary gland development, and seizures, the latter accompanied by abnormal development of the cerebellum. Most Msx2-mutant phenotypes, including calvarial defects, are enhanced by genetic combination with Msx1 loss of function, indicating that Msx gene dosage can modify expression of the PFM phenotype. Our results provide a developmental basis for PFM and demonstrate that Msx2 is essential at multiple sites during organogenesis.

Abnormalities, Multiple↗
PubMed2000

Child rotavirus infection in association with acute gastroenteritis in two Chinese sentinel hospitals.

Rotavirus gastroenteritis is an important pediatric disease in China. In a survey of rotavirus infection at two sentinel hospitals in China (Beijing Friendship Hospital and Changchun Children's Hospital), 296 cases were detected. A total of 283 (95.6%) cases of rotavirus infection occurred in children under 5 years of age. Serotype G1 (62%) was most prevalent followed by G2 (28.5%), G3 (5%) and G4 (2%). Mixed infections (n = 8, 3%) were rate, and 16 isolates (5.5%) remained non-typeable. A consistent epidemic occurred during the winter. Rotavirus was responsible for about 61.8% of diarrhea-related hospitalizations in children under 5 years of age, with a mean hospital stay of 5.6 days (1.0-21 days). The estimated rate of rotavirus-attributed hospitalizations was 16/1000 children under 5 years of age per year. Rotavirus-related death is rare in Changchun and Beijing. The present findings suggest that a rotavirus vaccine for the prevention of severe disease and a reduction of treatment costs would be of significant benefit to China.

Child, Preschool↗
PubMed2000

Plasminogen activator inhibitor-1 expression is regulated by the angiotensin type 1 receptor in vivo.

BACKGROUND: The fibrinolytic system plays an important role in degrading fibrin-rich thrombi and in vascular and tissue remodeling. Elevated levels of plasminogen activator inhibitor-1 (PAI-1) can reduce the efficiency of the endogenous fibrinolytic system. Angiotensin (Ang) has been shown to regulate PAI-1 expression via the Ang type 1 (AT1) receptor in some tissues and via the AT4 receptor in cultured endothelium. The purpose of this study was to examine the tissue-specific pattern of PAI-1 expression in response to infusion of Ang II in vivo. METHODS: Adult male Sprague-Dawley rats (N = 5 in each group) were treated with four hours of intravenous infusions of Ang II or vehicle control while mean arterial pressure (MAP) was monitored: group 1, 600 ng/kg/min Ang II; group 2, Ang II + 10 mg/kg of the AT1 receptor antagonist (AT1RA) L158-809 q2 hour; group 3, Ang II + 0.01 to 0.1 mg/kg hydralazine as required to maintain normal blood pressure; and group 4, saline-infused controls. After infusion, tissue was harvested for Northern blotting, immunohistochemical analysis, and in situ hybridization. RESULTS: In group 1, Ang II infusion increased MAP from 105 +/- 8 to 160 +/- 9 mm Hg (mean +/- SE, P < 0. 01). Ang II induced increased expression of PAI-1 mRNA in all tissues examined from 5.1-fold in the heart, 9.7-fold in the kidney, 10.0-fold in the aorta, and up to 30.0-fold in the liver (all P < 0. 01 vs. control). While both AT1RA (group 3) and hydralazine (group 4) prevented Ang II-induced elevation in blood pressure, the Ang II-dependent expression of PAI-1 mRNA was reduced by only AT1 receptor blockade. CONCLUSIONS: We conclude that in the rat, PAI-1 is induced in a variety of tissues by Ang II directly through the AT1 receptor, independent of its effects on blood pressure.

Angiotensin II↗
PubMed2000

Aldosterone modulates plasminogen activator inhibitor-1 and glomerulosclerosis in vivo.

BACKGROUND: Aldosterone promotes nephrosclerosis in several rat models, whereas aldosterone receptor antagonism blunts the effect of activation of the renin-angiotensin-aldosterone system (RAAS) on nephrosclerosis, independent of effects on blood pressure. Based on recent findings linking activation of the RAAS with impaired fibrinolytic balance, we hypothesized that aldosterone induces sclerosis through effects on plasminogen activator inhibitor-1 (PAI-1), the major physiological inhibitor of plasminogen activation. METHODS: We examined the effect of aldosterone antagonism on the development of sclerosis and on renal PAI-1 expression following radiation injury in the rat. Following a single dose of 12 Gy to the kidneys, male Sprague-Dawley rats were treated with placebo, the aldosterone antagonist spironolactone (4.5 mg/day by time-release subcutaneous pellet), the angiotensin type 1 receptor antagonist L158-809 (AT1RA; 80 mg/L drinking water), or combined spironolactone and AT1RA. RESULTS: Rats treated with placebo developed significant proteinuria and nephrosclerosis 12 weeks following radiation associated with hypertension. Kidney PAI-1 mRNA expression was increased eightfold (P < 0.001 vs. nonradiated controls). Spironolactone alone had no effect on blood pressure (systolic blood pressure 149.0 +/- 5.4 mm Hg) compared with placebo (151.6 +/- 11.2 mm Hg, P = NS), whereas AT1RA alone (107.7 +/- 8.9 mm Hg, P = 0.013 vs. placebo) or in combination therapy (102.1 +/- 6.2 mm Hg, P = 0.001 vs. placebo) lowered blood pressure. Both the AT1RA and spironolactone decreased proteinuria following radiation (P < 0.001 vs. placebo for either drug), and the combination of AT1RA + spironolactone had a greater effect on proteinuria than spironolactone alone (P = 0.003). Aldosterone antagonism significantly decreased (P = 0.016 vs. placebo) and AT1RA virtually abolished (P = 0.001 vs. placebo) the development of sclerosis. Spironolactone significantly decreased PAI-1 mRNA expression in the kidneys of radiated animals (PAI-1 mRNA/GAPDH ratio 0.39 +/- 0.13 vs. placebo 0.84 +/- 0.05, P = 0.006), and there was a significant correlation between the degree of sclerosis and the level of PAI-1 immunostaining within individual rats (R2 = 0.97, P < 0.0001). CONCLUSION: This study is, to our knowledge, the first to demonstrate that aldosterone regulates PAI-1 expression in vivo, and supports the hypothesis that aldosterone induces renal injury through its effects on PAI-1 expression.

Aldosterone↗
PubMed2000

Cellular pharmacology of the D- and L-enantiomers of beta-5-o-carboranyl-2'-deoxyuridine.

The cellular pharmacology of the D- and L-enantiomers of beta-5-o-carboranyl-2'-deoxyuridine (CDU), compounds designed for boron neutron capture therapy (BNCT), were studied using human CEM lymphoblast and U-251 glioblastoma cells, at a physiologically achievable concentration (1 microM). Accumulation of the enantiomers was rapid and indistinguishable, reaching cellular concentrations > 40-fold higher than extracellular levels, with approximately 5% persisting in cells after incubation in fresh medium for more than 2 hr. Uptake was not affected by nucleoside uptake inhibitors, but was inhibited by the purine base uptake inhibitor papaverine.

Biological Transport↗
PubMed2000

An efficient method of measuring the 4 mm helmet output factor for the Gamma knife.

It is essential to have accurate measurements of the 4 mm helmet output factor in the treatment of trigeminal neuralgia patients using the Gamma Knife. Because of the small collimator size and the sharp dose gradient at the beam focus, this measurement is generally tedious and difficult. We have developed an efficient method of measuring the 4 mm helmet output factor using regular radiographic films. The helmet output factor was measured by exposing a single Kodak XV film in the standard Leksell spherical phantom using the 18 mm helmet with 30-40 of its plug collimators replaced by the 4 mm plug collimators. The 4 mm helmet output factor was measured to be 0.876 +/- 0.009. This is in excellent agreement with our EGS4 Monte Carlo simulated value of 0.876 +/- 0.005. This helmet output factor value also agrees with more tedious TLD, diode and radiochromic film measurements that were each obtained using two separate measurements with the 18 mm helmet and the 4 mm helmet respectively. The 4 mm helmet output factor measured by the diode was 0.884 +/- 0.016, and the TLD measurement was 0.890 +/- 0.020. The radiochromic film measured value was 0.870 +/- 0.018. Because a single-exposure measurement was performed instead of a double exposure measurement, most of the systematic errors that appeared in the double-exposure measurements due to experimental setup variations were cancelled out. Consequently, the 4 mm helmet output factor is more precisely determined by the single-exposure approach. Therefore, routine measurement and quality assurance of the 4 mm helmet output factor of the Gamma Knife could be efficiently carried out using the proposed single-exposure technique.

Film Dosimetry↗
PubMed2000

The effect of user-defined variables on dosimetry consistency in Gamma Knife planning.

We report a dosimetric variation caused by a user-defined variable for the Leksell Gamma Knife planning system. Treatment plans of 31 randomly selected patients were studied retrospectively to determine the dosimetric effects in the dose prescription and computation as a result of dose matrix positioning in the Leksell Gamma Plan (LGP, Version 4.12). Phantom studies with ion chamber measurements were carried out to validate the accuracy of the computation results. An average overdose of 2% was found due to the variations in the user-defined dose matrix position for the studied cases. In the extreme, the overdose value was as high as 5% with an over-treatment time exceeding 2 min. The phantom measurements were found to agree with the LGP calculation within 0.5%. An adaptive method was developed and demonstrated in this study to eliminate such dosimetry variations.

Biophysical Phenomena↗
PubMed2000

Monte Carlo verification of IMRT dose distributions from a commercial treatment planning optimization system.

The purpose of this work was to use Monte Carlo simulations to verify the accuracy of the dose distributions from a commercial treatment planning optimization system (Corvus, Nomos Corp., Sewickley, PA) for intensity-modulated radiotherapy (IMRT). A Monte Carlo treatment planning system has been implemented clinically to improve and verify the accuracy of radiotherapy dose calculations. Further modifications to the system were made to compute the dose in a patient for multiple fixed-gantry IMRT fields. The dose distributions in the experimental phantoms and in the patients were calculated and used to verify the optimized treatment plans generated by the Corvus system. The Monte Carlo calculated IMRT dose distributions agreed with the measurements to within 2% of the maximum dose for all the beam energies and field sizes for both the homogeneous and heterogeneous phantoms. The dose distributions predicted by the Corvus system, which employs a finite-size pencil beam (FSPB) algorithm, agreed with the Monte Carlo simulations and measurements to within 4% in a cylindrical water phantom with various hypothetical target shapes. Discrepancies of more than 5% (relative to the prescribed target dose) in the target region and over 20% in the critical structures were found in some IMRT patient calculations. The FSPB algorithm as implemented in the Corvus system is adequate for homogeneous phantoms (such as prostate) but may result in significant under or over-estimation of the dose in some cases involving heterogeneities such as the air-tissue, lung-tissue and tissue-bone interfaces.

Computer Simulation↗