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Biomedical subjects

M K Yu

Publications and source records attributed to M K Yu.

At least 19 recordsLinked to original sources

Non-surgical management of microperforation induced by EMR of the stomach.

BACKGROUND: Perforation and bleeding are major complications associated with gastric endoscopic mucosal resection. Evident perforation during endoscopic mucosal resection can be managed by endoscopic clipping. However, management of microperforation is not well established. PATIENT AND METHOD: From January 2002 to June 2004, 109 early gastric cancers and 300 adenomas were treated with endoscopic mucosal resection. Iatrogenic perforations occurred in 4.16% (n=17) patients. Following exclusion of four evident perforations, microperforation was observed in 3.18% (n=13) patients. The clinical features of microperforation in patients were retrospectively reviewed. RESULTS: In a total of 13 microperforation cases, 2 patients were managed surgically. The remaining patients successfully recovered without surgical management. In the case of 11 patients without surgery, 7 experienced abdominal pain, which required analgesics, 2 patients experienced mild discomfort and 2 patients experienced no symptoms. A body temperature above 37.5 degrees C was observed in 9.1% (n=1) patients and leucocytosis above 9000 microL-1 was in 72.7% (n=8) patients. The mean duration of nasogastric tube drainage was 2.36+/-1.03 days, of fasting 4.18+/-1.17 days, of intravenous antibiotics 5.55+/-1.44 days and of hospitalisation 7.45+/-1.04 days. CONCLUSION: Microperforation induced by gastric endoscopic mucosal resection can be managed successfully using a non-surgical approach including fasting, nasogastric tube drainage and intravenous antibiotics.

Abdominal Pain↗

HAb18G/CD147-mediated calcium mobilization and hepatoma metastasis require both C-terminal and N-terminal domains.

HAb18G/CD147 is a heavily glycosylated protein containing two immunoglobulin superfamily domains. Our previous studies have indicated that overexpression of HAb18G/CD147 enhances metastatic potentials in human hepatoma cells by disrupting the regulation of store-operated Ca2+ entry by nitric oxide (NO)/cGMP. In the present study, we investigated the structure-function of HAb18G/CD147 by transfecting truncated HAb18G/CD147 fragments into human 7721 hepatoma cells. The inhibitory effect of HAb18G/CD147 on 8-bromo-cGMP-regulated thapsigargin-induced Ca2+ entry was reversed by the expression of either C or N terminus truncated HAb18G/CD147 in T7721deltaC and T7721deltaN cells, respectively. The potential effect of HAb18G/CD147 on metastatic potentials, both adhesion and invasion capacities, of hepatoma cells was abolished in T7721deltaC cells, but not affected in T7721deltaN cells. Release and activation of matrix metalloproteinases (MMPs), MMP-2 and MMP-9, were found to be enhanced by the expression of HAb18G/CD147, and this effect was abolished by both truncations. Thapsigargin significantly enhanced release and activation of MMPs (MMP-2 and MMP-9) in non-transfected 7721 cells, and this effect was negatively regulated by SNAP. However, no effects of thapsigargin or SNAP were observed in T7721 cells, and expression of HAb18G/CD147 enhanced secretion and activation of MMPs at a stable and high level. Taken together, these results suggest that both ectodomain and intracellular domains of HAb18G/CD147 are required to mediate the effect of HAb18G/CD147 on the secretion and activation of MMPs and metastasis-related processes in human hepatoma cells by disrupting the regulation of NO/cGMP-sensitive intracellular Ca2+ mobilization although each domain may play different roles.

Antigens, CD↗

Expression, immunolocalization, and functional activity of Na+/H+ exchanger isoforms in mouse endometrial epithelium.

The luminal fluid microenvironment of the uterus is important for sperm capacitation and embryo development. In an attempt to understand the possible role of Na(+)/H(+) exchangers (NHEs) in uterine function, the mRNAs of different NHE isoforms as well as their subcellular localization (apical versus basolateral) and functional activity were investigated in mouse endometrial epithelial cells using reverse transcriptase-polymerase chain reaction (RT-PCR), immunohistochemistry, and intracellular pH (pH(i)) measurement techniques. The presence of NHE1, NHE2, and NHE4, but not NHE3 mRNAs were revealed by RT-PCR. Immunostaining showed that NHE1, NHE2, and NHE4 were present in both apical and basolateral membranes. The pH(i) recovery from intracellular acidification was Na(+)-dependent; however, the rate of pH(i) recovery depending on basolateral Na(+) was 12.4 times faster than that depending on apical Na(+). The Na(+)-dependent rate of pH(i) recovery was also inhibited by amiloride, indicating H(+) extrusion through NHEs; however, the amiloride sensitivity of the apical membrane was less than that of the basolateral membrane, suggesting the involvement of different types of NHEs in the two membranes. The results indicate that the basolaterally located NHE1, NHE2, and NHE4, in addition to participating in the homeostatic control of intracellular pH, may play a role in H(+) extrusion in order to achieve transepithelial HCO(3)(-) secretion. The apically located NHEs may be involved in mediating Na(+) absorption as alternatives of or complementary to epithelial Na(+) channels.

Animals↗

Involvement of Na+-HCO3- cotransporter in mediating cyclic adenosine 3',5'-monophosphate-dependent HCO3- secretion by mouse endometrial epithelium.

The present study investigated the involvement of Na+-HCO3- cotransporter in mediating cAMP-stimulated HCO3- secretion across the cultured mouse endometrial epithelium using the short-circuit current (I(SC)) technique and intracellular pH measurement. Forskolin stimulated a rise in the I(SC), 55.6% and 52.1% of which could be reduced by the removal of extracellular Cl- or by eliminating the contribution of Cl- secretion by bumetanide, an inhibitor of Na+-K+-2Cl- cotransporter, respectively. More than 80% reduction in the forskolin-induced I(SC) was obtained when both Cl- and HCO3- in the bath were removed or in HCO3--free solution with bumetanide, indicating that the I(SC) depended on both Cl- and HCO3-. The presence of the Na+ channel-blocker amiloride in the apical solution did not reduce the forskolin-induced I(SC); however, the I(SC) could be abolished by removing Na+ from the bathing solution, suggesting that the Cl-- and HCO3--dependent I(SC) was also dependent on basolateral Na+. The forskolin-stimulated I(SC) could be reduced 43.6% by removal of HCO3- and 47.9% by a Na+-HCO3--cotransporter inhibitor, dihydrogen-4,4'-didsothiocyanostilbene-2,2'-disulfonic acid (H2DIDS). The inhibitory effect of H2DIDS was observed in Cl--free solution, but not when HCO3- was removed, thus confirming its effect on HCO3--dependent transport. Intracellular pH measurements demonstrated that the recovery from cellular acidification depended on the presence of both basolateral Na+ and HCO3-, further indicating the involvement of Na+-HCO3- cotransporter. Reverse transcription-polymerase chain reaction experiments confirmed the expression of Na+-HCO3- cotransporter in the mouse endometrium. The results suggest that basolaterally located Na+-HCO3- cotransporter is involved in mediating cAMP-stimulated HCO3- secretion across the mouse endometrial epithelium.

4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid↗

Analytical representation of enhanced dynamic wedge factors for symmetric and asymmetric photon fields.

The Enhanced Dynamic Wedge (EDW) presents many advantages over the physical wedge. However, in order to calculate monitor units (MUs) necessary to deliver a certain dose at a certain point, EDW factors (EDWFs) need to be determined. In this work, based on analysis of the golden segmented treatment table (GSTT) and the MU fraction model, an empirical analytic formula has been developed to calculate EDW factors for symmetric and asymmetric fields. This formalism is an extension of the MU fraction model. However in comparison with previous studies [J. P. Gibbons, Med. Phys. 25, 1411-1418 (1998) and M. Miften et al., Med. Dosim. 25, 81-86 (2000)], this formula is simpler, and easier to use. It is applicable to EDW fields of different sizes, wedge angles and different photon energies. For 6 and 18 MV beams from a Varian 21EX accelerator with 7 EDW angles (Varian Oncology Systems, Palo Alto, CA), more than 250 measured EDWFs for symmetric and asymmetric fields with different off-axis distances and field sizes were compared with model calculations. Results show that 80% and 98% of calculated EDWFs match corresponding measured values to within 0.5% and 1.0%, respectively, the maximum deviation being 1.3%.

Algorithms↗

Synthesis of P(1)-Citronellyl-P(2)-alpha-D-pyranosyl pyrophosphates as potential substrates for the E. coli undecaprenyl-pyrophosphoryl-N-acetylglucoseaminyl transferase MurG.

P(1)-Citronellyl-P(2)-alpha-D-pyranosyl pyrophosphates containing alpha-D-N-acetylglucoseaminyl, alpha-D-glucosyl, and alpha-D-N-acetylmuramyl carbohydrates were synthesized and used in substrate specificity studies of the Escherichia coli MurG enzyme. Oxalyl chloride activation of citronellyl phosphate for coupling to alpha-D-pyranose-1-phosphates resulted in markedly improved yields over traditional Khorana-Moffatt and diphenyl chlorophosphate activation strategies.

Bacterial Outer Membrane Proteins↗

The involvement of HAb18G/CD147 in regulation of store-operated calcium entry and metastasis of human hepatoma cells.

The present study examined the effect of hepatoma-associated antigen HAb18G (homologous to CD147) expression on the NO/cGMP-regulated Ca(2+) mobilization and metastatic process of human hepatoma cells. HAb18G/CD147 cDNA was transfected into human 7721 hepatoma cells to obtain a cell line stably expressing HAb18G/CD147, T7721, as demonstrated by Northern blot and immunocytochemical studies. 8-Bromo-cGMP (cGMP) inhibited the thapsigargin-induced Ca(2+) entry in a concentration-dependent manner in 7721 cells. The cGMP-induced inhibition was abolished by an inhibitor of protein kinase G, KT5823 (1 microm). However, expression of HAb18G/CD147 in T7721 cells decreased the inhibitory response to cGMP. A similar concentration-dependent inhibitory effect on the Ca(2+) entry was observed in 7721 cells in response to a NO donor, (+/-)-S-nitroso-N-acetylpenicillamine (SNAP). The inhibitory effect of SNAP on the thapsigargin-induced Ca(2+) entry was significantly reduced in HAb18G/CD147-expressing T7721 cells, indicating a role for HAb18G/CD147 in NO/cGMP-regulated Ca(2+) entry. Experiments investigating metastatic potentials demonstrated that HAb18G/CD147-expressing T7721 cells attached to the Matrigel-coated culture plates and invaded through Matrigel-coated permeable filters at the rate significantly greater than that observed in 7721 cells. Both the attachment and invasion rates could be suppressed by SNAP, and the inhibitory effect of SNAP could be reversed by NO inhibitor, N(G)-nitro-l-arginine methyl ester. The sensitivity of the attachment and invasion rates to cGMP was significantly reduced in T7721 cells as compared with 7721 cells when cells were pretreated with thapsigargin. The difference in the sensitivity between the two cells could be abolished by a Ca(2+) channel blocker, Ni(2+) (3 mm). These results suggest that HAb18G/CD147 enhances metastatic potentials in human hepatoma cells by disrupting the regulation of store-operated Ca(2+) entry by NO/cGMP.

Alkaloids↗

cGMP-regulated store-operated calcium entry in human hepatoma cells.

This study aimed to investigate cGMP-regulated store-operated Ca(2+)entry in human 7721 hepatoma cells. [Ca(2+)](i)was measured using Fura2/AM. After incubation of the cells with 4 microm thapsigargin, Ca(2+)entry was evoked by application of 1 mMm Ca(2+)to extracellular solution and was blocked by 3 m m Ni(2+), indicating the presence of store-operated Ca(2+)entry in human 7721 hepatoma cell line. Application of 8-Br-cGMP reduced the [Ca(2+)](i)in hepatoma 7721 cells by 80%. These data demonstrated for the first time that store-operated Ca(2+)entry pathway is present in human hepatoma cells, which is regulated by cGMP.

Calcium↗

Detection of occult cobalamin deficiency by magnetic resonance imaging.

We present a case of cobalamin deficiency in an elderly woman who presented with peripheral neuropathy without evidence of anemia or macrocytosis; her diagnosis was suspected with cervical magnetic resonance imaging. This imaging modality may identify patients with cobalamin deficiency who have neurologic abnormalities with normal hematologic parameters.

Aged↗

Synergy and duality in peptide antibiotic mechanisms.

The molecular mechanisms by which peptide antibiotics disrupt bacterial DNA synthesis, protein biosynthesis, cell wall biosynthesis, and membrane integrity are diverse, yet historically have been understood to follow a theme of one antibiotic, one inhibitory mechanism. In the past year, mechanistic and structural studies have shown a rich diversity in peptide antibiotic mechanism. Novel secondary targeting mechanisms for peptide antibiotics have recently been discovered, and the mechanisms of peptide antibiotics involved in synergistic relationships with antibiotics and proteins have been more clearly defined. In apparent response to selective pressures, antibiotic-producing organisms have elegantly integrated multiple functions and cooperative interactions into peptide antibiotic design for the purpose of improving antimicrobial success.

Amino Acid Sequence↗

Evaluation of a commercial three-dimensional electron beam treatment planning system.

We evaluated a commercial three-dimensional (3D) electron beam treatment planning system (CADPLAN V.2.7.9) using both experimentally measured and Monte Carlo calculated dose distributions to compare with those predicted by CADPLAN calculations. Tests were carried out at various field sizes and electron beam energies from 6 to 20 MeV. For a homogeneous water phantom the agreement between measured and CADPLAN calculated dose distributions is very good except at the phantom surface. CADPLAN is able to predict hot and cold spots caused by a simple 3D inhomogeneity but unable to predict dose distributions for a more complex geometry where CADPLAN underestimates dose changes caused by inhomogeneity. We discussed possible causes for the inaccuracy in the CADPLAN dose calculations. In addition, we have tested CADPLAN treatment monitor unit and electron cut-out factor calculations and found that CADPLAN predictions generally agree with manual calculations.

Algorithms↗

Effect of beam blocking on linac head scatter factors.

PURPOSE: This study aimed to investigate the influence of beam blocking on head scatter within the context of a two-component x-ray source model. METHODS AND MATERIALS: Head scatter factors were measured for open rectangular fields defined by X and Y jaws and for fields blocked by a multileaf collimator (MLC) for a 6-MV photon beam from a Varian 2300CD accelerator. A simple formula based on consideration of linac head geometry and an x-ray source model was derived to determine when the head scatter factor for a shaped field depends only on jaw settings and when it is influenced by the blocking (cerrobend blocks or MLC) itself. RESULTS: Experimental data demonstrate that the assumption that head scatter is unaffected by the introduction of beam blocking is not always acceptable, particularly for fields blocked by an MLC. The ratios of open to blocked field dimensions were compared with simple functions characterizing the accelerator head geometry to predict changes in the behavior of head scatter factors observed experimentally. CONCLUSION: A simple formula can be used to determine when head scatter factors are influenced by beam blocking (cerrobend blocks or MLC).

Equipment Design↗

Linear accelerator photon beam quality at off-axis points.

Transmitted intensity through water was measured in a narrow-beam geometry for different energy x-ray beams from commercial accelerators. In order to accurately obtain the attenuation coefficient of the incident beam using transmission data, a novel formula was developed based on consideration of beam hardening in phantom. The value of the attenuation coefficient obtained by fitting transmission data to this formula was found to be independent of the absorber thickness used in experiments, whereas the attenuation coefficient obtained from the traditional formula, I(x) = I0 exp(-mux), changed by up to 7% with absorber thickness for a given beam. The beam hardening coefficient obtained from our formula indicates that the attenuation coefficient in water changes by about 0.33% per cm near the surface for the high-energy photon beams studied. Variations in beam quality with off-axis distance were subsequently investigated using the new formula. Results show that the attenuation coefficient at the water surface increased by about 15% for 15 and 18 MV beams, and by 11%-13% for 6 MV beams, when the off-axis distance at 100 cm from the source was changed from 0 to 18 cm. Consideration of the physics of bremsstrahlung production suggests that these variations should be mainly determined by the shape of the flattening filter, i.e., by the path length of rays traversing the filter in different directions. This expectation was confirmed by observing that the attenuation coefficient at the phantom surface can be related to the ray path of the beam in the flattening filter using the new transmission formula.

Biophysical Phenomena↗

Prostaglandin F2 alpha stimulates hypertrophic growth of cultured neonatal rat ventricular myocytes.

Prostaglandin F2 alpha (PGF2 alpha) stimulates protein synthesis of skeletal and smooth muscle cells in culture and is elevated in the heart during compensatory growth. We hypothesized that PGF2 alpha stimulates hypertrophic growth of neonatal rat cardiac myocytes. Prostaglandin F2 alpha increased [3H]phenylalanine incorporation by cultured ventricular myocytes in a dose-dependent manner (EC50 = 11 nM), suggesting action through a PGF-specific receptor. Semiquantitative reverse transcriptase polymerase chain reaction revealed that PGF receptor mRNA is expressed in ventricular myocytes > A7R5 vascular smooth muscle cells >> cardiac fibroblast-like cells. The protein content of cardiomyocyte cultures was increased by 10 nM PGF2 alpha and 11 beta-PGF2 alpha but was unchanged by 10 nM PGD2, PGE2, PGF1 alpha, carbaprostacyclin, U-46619, or 12- or 15-hydroxyeicosatrienoic acid. Stimulation of myofibrillar gene expression by PGF2 alpha was demonstrated by Northern and Western blot analysis for myosin light chain-2 (MLC-2) and by transient transfection experiments with MLC-2 luciferase expression plasmids. In addition, myofibrillogenesis was increased by PGF2 alpha as assessed by immunocytochemical staining with MLC-2 antisera. Prostaglandin F2 alpha did not affect myocyte proliferation or [3H]thymidine incorporation, thus myocyte growth occurred by hypertrophy. Proliferative and hypertrophic growth of cardiac fibroblast-like cells were unaffected by PGF2 alpha. We conclude that PFG2 alpha stimulates hypertrophic growth of neonatal rat ventricular myocytes in culture and speculate that PGF2 alpha plays a role in myocardial adaptation to chronic hypertrophic stimuli, recovery from injury, and cardiac ontogeny.

Animals↗

Measurement of photon beam backscatter from collimators to the beam monitor chamber using target-current-pulse-counting and telescope techniques.

Backscattered radiation (BSR) arising from field-defining collimators and entering the beam monitor chamber (BMC) may contribute to observed variations in medical linear accelerator photon beam output with collimator setting. Measuring the magnitude of such contributions for particular accelerators under specified operating conditions is therefore important when attempting to understand and model accelerator head scatter. The present work was conducted to confirm some backscatter measurements for collimating jaws reported previously and to extend these to include other accelerators and a multileaf collimator (MLC). BSR reaching the BMC from the jaws of Clinac 600C, 2100C and 2300CD accelerators and from an MLC on the 2300CD was investigated using both target-current-pulse-counting and telescope methods. Our measurements show that for the Clinac 600C BSR-dependent output variations are negligible. However, for the 2100C and 2300CD BSR-dependent relative output increased in an almost linear fashion, by up to 2.4% for 15 and 18 MV beams, and by up to 1.7% for 6 MV beams, as the field size varied from 5 x 5 cm2 to 40 x 40 cm2. The magnitude of BSR dependent upon collimator location in the head, as expected, thereby contributing to the collimator exchange effect. An earlier study at our centre using the telescope method had reported higher BSR levels. This discrepancy was resolved when corrections for telescope block and room scatter, previously assumed negligible, were made.

Humans↗

Analytical representation of head scatter factors for shaped photon beams using a two-component x-ray source model.

An analytic representation proposed for the relative intensity distribution of the extra-focal source in a two-component x-ray source model serves as the basis for calculation. From this representation, a closed-form expression for head scatter factors defined on the central beam axis is derived by integrating over the area of the extra-focal source plane visible from the measurement point. The resulting expression is applicable to photon beams from different Varian accelerators and different photon energies, and includes effects arising from beam shaping with cerrobend blocks or multileaf collimators (MLCs). For 6- and 15-MV photon beams from Varian 600C and 2300CD accelerators (Varian Oncology Systems, Palo Alto, CA), 361 measured head scatter factors for square, rectangular, asymmetric, and arbitrarily shaped fields, formed by either the X and Y jaws, the MLC and Y jaws, or by the MLC alone, were compared with model calculations. Results show that 93.4% of calculated values match corresponding experimental points to within 0.5%, the average deviation being 0.23% and the maximum deviation 0.9%. Thus, as a consequence of this work, the different influence of the X jaws, the Y jaws, and the MLC on head scatter factors is quantitatively described. In particular, it is demonstrated that in the case of radially symmetric scattering, the collimator exchange effect arises as a result of the different distances of the X and Y jaws from the focal spot.

Biophysical Phenomena↗