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Biomedical subjects

C H Kao

Publications and source records attributed to C H Kao.

At least 19 recordsLinked to original sources

P-Glycoprotein and multidrug resistance-related protein expressions in relation to technetium-99m methoxyisobutylisonitrile scintimammography findings.

The purpose of this study was to retrospectively study 48 patients with infiltrating ductal breast cancer to evaluate the relationship between the degree of accumulation of technetium-99m methoxyisobutylisonitrile (Tc-MIBI) and P-glycoprotein (Pgp) or multidrug resistance-related protein (MRP) expression in breast cancer tissues. Before surgery or biopsy, all 48 patients underwent scintimammography started 10 min after the injection of Tc-MIBI. Tumor:background (T:B) ratios were calculated from the Tc-MIBI scintimammography. Immunohistochemical analysis was performed on the pathological specimens of the 48 breast tumors to determine Pgp and MRP expression. According to the results of immunohistochemical analysis, the 48 breast cancers were separated into four groups: (a) group 1, 12 cancers with both positive Pgp expression and positive MRP expression; (b) group 2, 12 cancers with positive Pgp expression and negative MRP expression; (c) group 3, 12 cancers with negative Pgp expression and positive MRP expression; and (d) group 4, 12 cancers with both negative Pgp expression and negative MRP expression. Among the four groups, the T:B ratio was lowest in group 1 (1.13+/-0.10) and highest in group 4 (2.17+/-0.14), respectively (P < 0.05). The T:B ratios of groups 2 (1.30+/-0.25) and 3 (1.32+/-0.26) were between those of groups 1 and 4. Our data confirmed that Tc-MIBI scintimammography is useful for determining Pgp and MRP expression in patients with breast cancers.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

Small intestinal bacterial overgrowth versus antimicrobial capacity in patients with spontaneous bacterial peritonitis.

BACKGROUND: Spontaneous bacterial peritonitis (SBP) is a serious infection in cirrhotic patients with ascites. Both defects in the host defense mechanisms and the enhancement of the offensive factor (small intestinal bacterial overgrowth (SIBO)) may contribute to the development of SBP. Therefore, the aim of this study was to evaluate the role of SIBO versus various antimicrobial capacities in the pathogenesis of SBP in cirrhotic patients. METHODS: Forty-five cirrhotic patients were enrolled in this study. Bacterial overgrowth was evaluated by breath hydrogen test (BH2T). The hepatic reticuloendothelial system phagocytic index (HRESPI) was measured by intravenously injected colloid suspensions. RESULTS: The Child-Pugh scores in the SBP group were higher than in the non-SBP group (10.5 +/- 2.0 versus 8.0 +/- 1.8, P < 0.01). The ascitic protein concentration was significantly lower in the SBP group than in the non-SBP group (897 +/- 425 mg/l versus 1,325 +/- 453 mg/l, P < 0.01). Furthermore, the serum C3 concentration was lower in the SBP group than in the non-SBP group (43.1 +/- 13.6 ng/dl versus 73.2 +/- 26.4 ng/dl, P < 0.01). The serum C4 concentration was also lower in the SBP group than in the non-SBP group (12.4 +/- 4.0 ng/dl versus 16.9 +/- 6.6 ng/dl, P < 0.05). The incidence of SIBO was higher in the SBP group than in the non-SBP group (68.2% versus 17.4%, P < 0.01). HRESPI values were significantly higher in the two groups of cirrhotic patients than in the normal reference. However, there were no statistical differences in HRESPI between the two groups (8.4 +/- 2.8 min in the SBP group versus 7.9 +/- 2.8 min in the non-SBP group). CONCLUSIONS: The results of this study showed that the hepatic reticuloendothelial function is impaired in cirrhotic patients, but the degree of impairment does not differ between patients with and without previous history of SBP. Lower ascitic total protein, lower serum C3 and C4 concentrations, and presence of SIBO are all risk factors for SBP. Based on the results of our study, defects in the host defense mechanisms and the enhancement of the offensive factor (SIBO) may act in concert for the development of SBP.

Ascitic Fluid↗

Paclitaxel-Based chemotherapy for non-small cell lung cancer: predicting the response with 99mTc-tetrofosmin chest imaging.

UNLABELLED: The purpose of this study was to retrospectively predict the chemotherapeutic response to paclitaxel for non-small cell lung cancer (NSCLC) using 99mTc-tetrofosmin (TF) uptake and to detect the expression of 170-kDa multidrug resistance-mediated P-glycoprotein (MDR-Pgp). METHODS: Before chemotherapy with paclitaxel, 20 patients with stage IIIb or IV NSCLC were enrolled in this study to undergo early and delayed 99mTc-TF chest imaging for calculating tumor-to-normal lung ratios (T/NL) and retention indices (RI) for assessment of the MDR-Pgp in NSCLC. RESULTS: The early and delayed mean T/NLs were 1.59 +/- 0.25 and 1.50 +/- 0.25, respectively, for 10 patients with a good response and 1.09 +/- 0.09 and 1.03 +/- 0.05, respectively, for 10 patients with a poor response. The differences were shown to be significant (P < 0.001) by independent Student t tests. However, no significant differences (P = 0.801) between good-response patients (-5.70% +/- 3.67%) and poor-response patients (-5.23% +/- 4.51%) were found in RI. In addition, other prognostic factors (age, sex, tumor size, stage, and cell type) were not significantly different between good-response patients and poor-response patients. CONCLUSION: 99mTc-TF chest images are potential tools for understanding MDR-Pgp expression in NSCLC and for predicting the chemotherapeutic response to paclitaxel.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

Expression of mediated P-glycoprotein multidrug resistance related to Tc-99m MIBI scintimammography results.

We prospectively studied a total of 24 patients with breast cancer to evaluate the relationship between the degree of accumulation of technetium-99m sestamibi (Tc-99m MIBI) and p-glycoprotein (Pgp) expression in tumor tissues. All 24 patients underwent Tc-99m MIBI scintimammography before surgery or biopsy. Immunohistochemical studies were performed on multiple non-consecutive sections of the same tumor using a Pgp specific monoclonal antibody, JSB-1. Planar images were started 10 min after injection of Tc-99m MIBI. Tumor to background (T/B) ratios calculated from the planar images were correlated with Pgp expression as determined by immunohistochemical studies. The T/B ratios were significantly lower for tumors in eight patients with positive Pgp expression (Group 1) than in 16 patients with negative expression (Group 2) (1.40+/-0.11 and 2.76+/-0.60, P<0. 05). Our data confirmed that Tc-99m MIBI scintimammography is useful for determination of the presence of multidrug resistance due to Pgp expression in patients with breast cancer.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

Tuning metal-to-metal charge transfer of mixed-valence complexes containing ferrocenylpyridine and rutheniumammines via solvent donicity and substituent effects.

A homogeneous series of heterobimetallic complexes of [R-Fc(4-py)Ru(NH3)5](PF6)2 (R = H, Et, Br, acetyl; Fc(4-py) = 4-ferrocenylpyridine) have been prepared and characterized. The mixed-valence species generated in situ using ferrocenium hexafluorophosphate as the oxidant show class II behavior, and the oxidized sites are ruthenium centered. deltaE(1/2), E(1/2)(Fe(III)/Fe(II)) - E(1/2)(Ru(III)/Ru(II)), an upper limit for deltaGo that is an energetic difference between the donor and acceptor sites, changes sharply and linearly with Gutmann solvent donor number (DN) and Hammett substituent constants (sigma). The solvent-dependent and substituent-dependent intervalence transfer bands were found to vary almost exclusively with deltaE(1/2). The activation energy for the optical electron transfer versus deltaE(1/2) plot yields a common nuclear reorganization energy (lambda) of 0.74 +/- 0.04 eV for this series. The equation that allows one to incorporate the effect of both solvent donicity and substituents on optical electron transfer is Eop = lambda + deltaGo, where deltaGo = (deltaGo)intrinsic + (deltaGo)solvent donicity + (deltaGo)substituent effect (deltaGo )intinnsic with a numerical value of 0.083 +/- 0.045 eV was obtained from the intercept of the deltaE(1/2) of [H-Fc(4-py)Ru(NH3)5]2+,3+,4+ versus DN plot. (deltaGo)solvent donicity was obtained from the average slopes of the deltaE(1/2) of [R-Fc-(4-py)Ru(NH3)5]2+,3+,4+ versus DN plot, and (deltaGo)substituent effect was obtained from the average slopes of the corresponding deltaE(1/2) versus sigma plot. The empirical equation allows one to finely tune Eop of this series to Eop = 0.82 + 0.019(DN) + 0.44sigma eV at 298 K, and the discrepancy between the calculated and experimental data is less than 6%.

Journal Article↗

Tissue polypeptide specific antigen and squamous cell carcinoma antigen for early prediction of recurrence in lung squamous cell carcinoma.

One of the major problems in the follow-up of patients with lung cancer is the early detection of recurrent disease. Tumor markers have been found helpful in detecting early recurrent disease. The aims of this study were to evaluate and compare the clinical usefulness of serial and simultaneous measurement of tissue polypeptide antigen (TPS) and squamous cell carcinoma (SCC) antigen for the early prediction of recurrence in patients with SCC of the lung. Sixty patients with SCC of the lung, including 25 patients with recurrence and 35 patients without recurrence after 1 year's follow-up after surgery, were enrolled in this study. The serial serum levels of TPS and SCC antigen were measured before surgery and 1 week, 1 month, 3 months, 6 months, 9 months, and 12 months after the operation for early detection of recurrence. The results revealed that (1) the mean serum values of TPS were significantly greater at all times after surgery in the 25 patients with recurrent SCC compared with the 35 patients without recurrent SCC, and (2) the mean serum values of SCC antigen were significantly greater only at 9 and 12 months after surgery in the 25 patients with recurrent SCC compared with the 35 patients without recurrent SCC. We conclude that TPS is a better marker than SCC antigen for early prediction of SCC recurrence in the lung.

Adult↗

Transient increase in alveolar epithelial permeability induced by volatile anesthesia with isoflurane.

Fifteen patients undergoing surgery and receiving volatile anesthesia with isoflurane were enrolled as the study group. At the same time, 15 patients undergoing surgery with intravenous anesthesia drugs were included as a control group to compare each other. Before surgery, 1 h after surgery, and 1 week after surgery, we investigated these two groups of patients with technetium-99m-labeled diethylene triamine pentaacetic acid radioaerosol inhalation lung scan (DTPA lung scan), a test to evaluate lung ventilation (LV), which was evaluated by the first and equilibrium lung ventilation image and alveolar epithelial permeability (AP) which was evaluated by the half time (T1/2, minutes) of Tc-99m DTPA radioaerosol lung clearance. No significant change and abnormality of LV before surgery, 1 h after surgery, or 1 week after surgery was found in either group of patients. In addition, no significant change in AP before surgery (T1/2 = 64.0 +/- 17.3 min), 1 h after surgery (64.5 +/- 19.6 min), or 1 week after surgery (63.6 +/- 17.6 min) was found among the control group patients (p values > 0.05). However, a significant transient increase in AP was found in the study group 1 h after surgery (71.7 +/- 17.5 versus 51.2 +/- 16.4 min), but it recovered 1 week after surgery (51.2 +/- 16.4 versus 70.9 +/- 16.0 min) (p values < 0.05). We conclude that volatile anesthesia with isoflurane can induce transient increase of AP.

Administration, Inhalation↗

Decreased salivary function in patients with end-stage renal disease requiring hemodialysis.

It has been speculated that impaired salivary flow is common in patients with end-stage renal disease (ESRD) requiring hemodialysis (HD). The aim of this study is to investigate the relation between oral manifestations and salivary function in patients with ESRD undergoing HD. Salivary function was measured by quantitative salivary scintigraphy in 60 patients with ESRD undergoing HD, as well as in 36 age- and sex-matched healthy controls for comparison. The 60 patients with ESRD undergoing HD were separated into two subgroups: group 1, 30 patients with oral manifestations, and group 2, 30 patients without oral manifestations. After an intravenous injection of 5 mCi of technetium 99m pertechnetate, sequential images at 1 minute per frame were acquired for 30 minutes. The 1- and 15-minute uptake ratios were calculated as the tracer uptakes in the four major salivary glands over the background regions of interest. Saliva excretion was stimulated by one 200-mg tablet of ascorbic acid administered orally 15 minutes post-tracer injection, then the maximal excretion ratios of the four major salivary glands were calculated. Our results show significantly poorer salivary function in patients with ESRD with oral manifestations compared with patients with ESRD without oral manifestations and healthy controls by means of objective and quantitative salivary scintigraphy.

Female↗

Methylprednisolone increases plasma leptin levels in Graves' hyperthyroidism patients with active Graves' ophthalmopathy.

Whether leptin, a product of the ob gene, can be stimulated by glucocorticoid administration has been an issue of controversy. We investigated the effect of intravenous administration of methylprednisolone (500 mg/day x 3 days) on plasma levels of leptin in 16 patients (female/male = 11/5) with Graves' hyperthyroidism and active ophthalmopathy who received pulse therapy. Significant elevation of plasma leptin levels started at the eighth hour (13.9+/-1.8 ng/mL, p=0.042) and lasted until the 72nd hour (21.2+/-5.0 ng/mL, p=0.009), as compared with basal levels (8.8+/-1.2 ng/mL). When methylprednisolone was replaced with oral prednisolone (10 mg three times per day x 2 weeks), no difference in plasma leptin levels was noted compared with basal measurement. Under methylprednisolone administration, a significant suppression of tumor necrosis factor-alpha began at the 24th hour (8.1+/-1.3 pg/mL, p=0.004) and lasted until the 48th hour (8.1+/-1.0 pg/mL, p=0.008), as compared with basal measurement (12.5+/-1.5 pg/mL). Compared with basal levels (93+/-2 mg/dL), significant elevation in the plasma glucose level started at the third hour (135+/-10 mg/dL, p=0.000) and lasted until the 72nd hour (110+/-4 mg/dL, p=0.019). The timing of serum insulin elevation approximated that of plasma glucose (3 hours: 14+/-3 microU/mL, p=0.006) and lasted until the end of prednisolone administration (2 weeks: 12+/-2 microU/mL, p=0.044), when compared with basal levels (14+/-3 microU/mL). We concluded that the parental administration of pharmacological doses of methylprednisolone to patients with Graves' hyperthyroidism could acutely raise their plasma level of leptin.

Adult↗

Genetic architecture of a morphological shape difference between two Drosophila species.

The size and shape of the posterior lobe of the male genital arch differs dramatically between Drosophila simulans and D. mauritiana. This difference can be quantified with a morphometric descriptor (PC1) based on elliptical Fourier and principal components analyses. The genetic basis of the interspecific difference in PC1 was investigated by the application of quantitative trait locus (QTL) mapping procedures to segregating backcross populations. The parental difference (35 environmental standard deviations) and the heritability of PC1 in backcross populations (>90%) are both very large. The use of multiple interval mapping gives evidence for 19 different QTL. The greatest additive effect estimate accounts for 11. 4% of the parental difference but could represent multiple closely linked QTL. Dominance parameter estimates vary among loci from essentially no dominance to complete dominance, and mauritiana alleles tend to be dominant over simulans alleles. Epistasis appears to be relatively unimportant as a source of variation. All but one of the additive effect estimates have the same sign, which means that one species has nearly all plus alleles and the other nearly all minus alleles. This result is unexpected under many evolutionary scenarios and suggests a history of strong directional selection acting on the posterior lobe.

Animals↗

On the differences between maximum likelihood and regression interval mapping in the analysis of quantitative trait loci.

The differences between maximum-likelihood (ML) and regression (REG) interval mapping in the analysis of quantitative trait loci (QTL) are investigated analytically and numerically by simulation. The analytical investigation is based on the comparison of the solution sets of the ML and REG methods in the estimation of QTL parameters. Their differences are found to relate to the similarity between the conditional posterior and conditional probabilities of QTL genotypes and depend on several factors, such as the proportion of variance explained by QTL, relative QTL position in an interval, interval size, difference between the sizes of QTL, epistasis, and linkage between QTL. The differences in mean squared error (MSE) of the estimates, likelihood-ratio test (LRT) statistics in testing parameters, and power of QTL detection between the two methods become larger as (1) the proportion of variance explained by QTL becomes higher, (2) the QTL locations are positioned toward the middle of intervals, (3) the QTL are located in wider marker intervals, (4) epistasis between QTL is stronger, (5) the difference between QTL effects becomes larger, and (6) the positions of QTL get closer in QTL mapping. The REG method is biased in the estimation of the proportion of variance explained by QTL, and it may have a serious problem in detecting closely linked QTL when compared to the ML method. In general, the differences between the two methods may be minor, but can be significant when QTL interact or are closely linked. The ML method tends to be more powerful and to give estimates with smaller MSEs and larger LRT statistics. This implies that ML interval mapping can be more accurate, precise, and powerful than REG interval mapping. The REG method is faster in computation, especially when the number of QTL considered in the model is large. Recognizing the factors affecting the differences between REG and ML interval mapping can help an efficient strategy, using both methods in QTL mapping to be outlined.

Chromosome Mapping↗