Proteomic profiling of microbial transglutaminase-induced polymerization of milk proteins.

Microbial transglutaminase (MTGase)-induced polymerization of individual milk proteins during incubation was investigated using a proteomics-based approach. The addition of MTGase (0.25-2.0 units/mL) caused the milk proteins to polymerize after a 3-h incubation period. Sodium dodecyl sulfate-PAGE analysis showed that the total intensities of the protein bands that corresponded to α(S)-casein, ß-casein, and κ-casein decreased from 8,245.6, 6,677.2, and 586.6 arbitrary units to 1,911.7, 0.0, and 66.2 arbitrary units, respectively. Components with higher molecular weights were observed, and the intensity of these proteins increased after 3h of incubation. These results support that inter- or intramolecular crosslinking occurred in the casein proteins of MTGase-treated milk. Two-dimensional electrophoresis analysis indicated that isomers of ß-casein, κ-casein, a fraction of serum albumin, α(S1)-casein, α(S2)-casein, ß-lactoglobulin, and α-lactalbumin in the milk were polymerized following incubation with MTGase. In addition, MTGase-induced polymerization occurred earlier for ß-casein and κ-casein isomers than for other milk proteins.

Sentinel node detection with radiocolloid lymphatic mapping in early invasive cervical cancer.

We assessed the feasibility of sentinel lymph node detection using technicium-99 radiocolloid lymphatic mapping for predicting lymph node metastases in early invasive cervical cancer. Thirty patients with cervical cancer (stages IA2-IIA) underwent preoperative lymphoscintigraphy using technicium-99 intracervical injection and intraoperative lymphatic mapping with a handheld gamma probe. After dissection of the sentinel nodes, the standard procedure of pelvic lymph node dissection and radical hysterectomy was performed as usual. The sentinel node detection rate was 100% (30/30). There were seven (23.3%) cases of microscopic lymph node metastases on pathologic analysis. All of them had sentinel node involvement. Therefore, the sensitivity of sentinel node identification for prediction of lymph node metastases was 100%, and no false negative was found. Preoperative lymphoscintigraphy, coupled with intraoperative lymphatic mapping, located the sentinel nodes accurately in our study patients. This sentinel node detection method appears to be feasible for predicting lymph node metastases.

Comparison of CYFRA 21-1 and squamous cell carcinoma antigen in detecting nasopharyngeal carcinoma.

CYFRA 21-1 is a newly developed tumor marker that is especially useful for detecting squamous cell carcinoma (SCC) of the lung. Squamous cell carcinoma antigen is a proven tumor marker that is especially useful for detecting SCC of the cervix. Our aim in this study was to compare the clinical value of CYFRA 21-1 and SCC antigen in the detection of nasopharyngeal carcinoma (NPC). Serum levels of CYFRA 21-1 and SCC antigen were measured in 80 untreated NPC patients and 77 healthy controls. The cutoff values of CYFRA 21-1 and SCC antigen, determined at the 95th percentile of the 77 healthy controls, were 2.48 ng/mL and 1.49 ng/mL, respectively. The results revealed that the mean serum value of only CYFRA 21-1 was significantly higher in the 80 NPC patients than in the 77 healthy controls, and the detection sensitivity of CYFRA 21-1 for NPC was significantly higher than that of SCC antigen. In conclusion, our results suggest that CYFRA 21-1 is a better tumor marker than SCC antigen for detection of NPC.

Effect of imaging time on gallium renal scan.

AIM: Gallium renal imaging has been reported to be useful in monitoring disease activity and predicting the response to therapy in lupus nephritis. Gallium renal images are usually obtained 48 h after the injection of 67Ga citrate, but 72-h images sometimes are the only available pictures. The aim of the present study was to determine whether the time intervals from injection to imaging had any effect on the grading of gallium renal scintigraphy. METHODS: Fifty-five patients with lupus nephritis underwent gallium renal imaging at both 48 h and 72 h post-injection of 111 MBq of 67Ga citrate. The relative uptakes of 67Ga by the kidneys and the spine was judged visually on the analog images. Renal uptake was rated on a scale of 0-3. RESULTS: Fifty-three patients (96.3%) had the same grading of renal uptake in the 48-h and the 72-h images. Only two patients (3.7%) had a different grading in the 72-h images when compared to the 48-h images. The correlation between the 48-h renal uptake and 72-h renal uptake was excellent, with a Spearman R value of 0.94. No significant difference was noted between these two groups, with a P value of 0.76 (using a Wilcoxon matched pairs test). CONCLUSION: A gallium renal scan can be obtained either 48 h or 72 h after injecting 67Ga citrate. The imaging time did not interfere with the grading of renal uptake in lupus nephritis.

Intra-tumoural injection of 90Y microspheres into an animal model of hepatoma.

BACKGROUND: Intrahepatic arterial injection of 90Y glass microspheres (90Y microspheres) is a useful therapeutic modality for inoperative liver tumour. Recently, a new concept of interstitial radiotherapy in the treatment of hepatic malignancies has been carried out with even more encouraging results. However, information regarding this technique is still very rare. The purpose of this study was to analyse the kinetics and biodistribution of 90Y microspheres in rats with hepatic tumours following intra-tumoural injection. METHODS: Twenty male Sprague-Dawley rats with hepatoma were killed at 1 h, 24 h, 48 h and 72 h (five rats each time) after intra-tumoural injection of approximately 7.4 MBq of 90Y microspheres. Samples of various organs were obtained and used to calculate the tissue concentrations and radiation doses. RESULTS: Our data showed that the radioactivity in the tumour was very high throughout this study. The lung was the only organ other than the tumour which showed high radioactivity. The concentrations of radioactivity in other organs, such as normal liver, muscle, spleen, bone, testis, and whole blood were quite low throughout the study. CONCLUSION: Direct intra-tumoural injection of 90Y microspheres is extremely attractive as a clinical therapeutic alternative in hepatoma patients.

Quantifying the dietary potassium requirement of juvenile hybrid tilapia (Oreochromis niloticus x O. aureus).

An 8 week feeding trial was conducted to determine the dietary K requirement for juvenile hybrid tilapia (Oreochromis niloticus x O. aureus). Purified diets with eight levels (0, 1, 2, 3, 4, 5, 7, 10 g/kg diet) of supplemental K were fed to tilapia. Each diet was fed to three replicate groups of fish initially weighing a mean value of 0.77 (SE 0.01) g/fish in a closed, recirculating rearing system. Weight gain was higher (P < 0.05) in fish fed the diets supplemented with 2, 3 and 4 g K/kg diet than in fish fed diet with 10 g K/kg diet and the unsupplemented control diet. Gill Na+-K+ ATPase activity was highest in fish fed the diets supplemented with 1-3 g K/kg diet, followed by fish fed the diet with 5 g K/kg diet and lowest in fish fed the diet with 10 g K/kg diet. Whole-body K content in fish were generally increased as the dietary K supplementation level increased. Analysis by polynomial regression of weight gain and gill Na+-K+ ATPase activity and by linear regression of whole-body K retention of the fish indicated that the adequate dietary K concentration for tilapia is about 2-3 g/kg diet.

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.

Semi-quantitative evaluation of gallium-67 scintigraphy in lupus nephritis.

Within nuclear medicine there is a trend towards quantitative analysis. Gallium renal scan has been reported to be useful in monitoring the disease activity of lupus nephritis. However, only visual interpretation using a four-grade scale has been performed in previous studies, and this method is not sensitive enough for follow-up. In this study, we developed a semi-quantitative method for gallium renal scintigraphy to find a potential parameter for the evaluation of lupus nephritis. Forty-eight patients with lupus nephritis underwent renal biopsy to determine World Health Organization classification, activity index (AI) and chronicity index (CI). A delayed 48-h gallium scan was also performed and interpreted by visual and semi-quantitative methods. For semi-quantitative analysis of the gallium uptake in both kidneys, regions of interest (ROIs) were drawn over both kidneys, the right forearm and the adjacent spine. The uptake ratios between these ROIs were calculated and expressed as the "kidney/spine ratio (K/S ratio)" or the "kidney/arm ratio (K/A ratio)". Spearman's rank correlation test and Mann-Whitney U test were used for statistical analysis. Our data showed a good correlation between the semi-quantitative gallium scan and the results of visual interpretation. K/S ratios showed a better correlation with AI than did K/A ratios. Furthermore, the left K/S ratio displayed a better correlation with AI than did the right K/S ratio. In contrast, CI did not correlate well with the results of semi-quantitative gallium scan. In conclusion, semi-quantitative gallium renal scan is easy to perform and shows a good correlation with the results of visual interpretation and renal biopsy. The left K/S ratio from semi-quantitative renal gallium scintigraphy displays the best correlation with AI and is a useful parameter in evaluating the disease activity in lupus nephritis.

Comparison of 18-fluoro-2-deoxyglucose positron emission tomography and computed tomography in detection of cervical lymph node metastases of nasopharyngeal carcinoma.

Neck lymph nodes (LNs) from 18 patients with nasopharyngeal carcinoma (NPC) were evaluated with 18-fluoro-2-deoxyglucose positron emission tomography (FDG-PET). Eighteen NPC patients underwent head and neck FDG-PET and computed tomography (CT) for detection of suspected neck LN metastases. For final diagnosis, biopsies were taken from neck LNs with discordant findings between FDG-PET and CT. Meanwhile, standard uptake values (SUVs) of the FDG-PET images were calculated to differentiate metastatic LNs from benign LNs. A total of 90 neck LNs found on either FDG-PET or CT were evaluated. In addition to 27 concordant positive results and 42 concordant negative LN results, biopsy findings revealed 11 metastatic LNs that were detected by FDG-PET but not by CT. However, the SUVs of the 11 metastatic LNs and 7 benign LNs were not significantly different. The CT scanning showed positive findings for I metastatic LN with negative FDG-PET findings. In addition, the tumor stage was upgraded in 5 patients on the basis of FDG-PET findings. In comparison with CT, FDG-PET has a higher potential for detecting neck LN metastases of NPC and assessing NPC tumor stage.

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.

Acute and chronic effects of isosorbide-5-mononitrate administration on effective renal plasma flow and the renin-aldosterone system in cirrhotic patients.

BACKGROUND AND AIMS: Isosorbide-5-mononitrate (ISMO) has been shown to be effective in reducing the risk of variceal bleeding in patients with cirrhosis. However, recent studies have suggested that this drug compromises renal function. The present study was conducted to assess the acute and chronic effects of ISMO on effective renal plasma flow (ERPF) and the renin-aldosterone profile in cirrhotic patients. METHODS: Fifteen cirrhotic patients were included in the present study. The mean arterial pressure (MAP), heart rate (HR), serum renin concentration (SR), ERPF and plasma aldosterone concentration (PA) were checked before ISMO treatment (baseline study), after a single oral dose of 20 mg ISMO (acute effect study) and after 3 weeks of ISMO treatment (chronic effect study). RESULTS: Our data showed that the oral administration of a single dose (20 mg) of ISMO to cirrhotic patients was associated with significant decreases in ERPF (from 405.18 to 369.06 mL/min) and MAP (from 93.26 to 86.40 mmHg), and increases in HR (from 65.53 to 70.06 beats/min), SR (from 24.15 to 54.41 pg/mL), and PA (from 105.1 to 148.7 pg/mL). However, no significant changes were observed in HR, MAP, PA, SR, or ERPF after 3 weeks of ISMO treatment when compared with the baseline study. CONCLUSIONS: The administration of ISMO causes a decrease in ERPF in cirrhotic patients and its use in patients with renal impairment should be considered cautiously.

Effects of 90Y-microspheres on liver tumors: comparison of intratumoral injection method and intra-arterial injection method.

UNLABELLED: Internal radiation therapy using intrahepatic arterial injection of 90Y-labeled glass microspheres (90Y-microspheres) has proven to be a promising therapeutic modality for inoperative liver tumor. Recently, direct intratumoral injection of 90Y-microspheres has been performed with even more encouraging results. The purpose of this study was to compare the treatment efficacy of these 2 methods using 90Y-microspheres. METHODS: Forty-eight male rats, each bearing a hepatic tumor, were divided into 4 groups (12 rats in each group) to evaluate the efficacy of treatment. Group 1 received an intratumoral injection of 37 MBq (1 mCi) 90Y-microspheres. Group 2 received an intratumoral injection of 0.1 mL normal saline as the control group. Group 3 received an intra-arterial injection of 37 MBq (1 mCi) 90Y-microspheres. Group 4 received an intra-arterial injection of 0.1 mL normal saline as the control group. Tumor size was measured by liver sonography before injection as well as at 2 and 4 wk after injection. Survival time was calculated from the day of treatment to 2 mo after treatment by Kaplan-Meier survival analysis. The response rate was evaluated by the change in tumor size and survival time. Fisher's exact, 2-tailed test was used to compare response rates. RESULTS: In the rats treated by intratumoral injection of 90-Y-microspheres, 83.3% (10/12) showed a good response. In contrast, all 12 rats in the control group showed a poor response. The difference was significant (P < 0.00001). Eighty-three percent (10/12) of the rats survived >60 d after intratumoral injection of 90Y-microspheres, whereas only 25% (3/12) of the control rats survived >60 d. The difference was significant (P = 0.0068). In the rats treated by intra-arterial injection of 90Y-microspheres, 58.3% (7/12) showed a good response to the treatment. All rats in the control group showed a poor response. The difference was significant (P = 0.0023). Sixty-six percent (8/12) of the rats survived >60 d after intra-arterial injection of 90Y-microspheres, whereas only 16.7% (2/12) of the control rats survived >60 d. The difference was significant (P = 0.0385). However, the response rate and survival time between the intratumoral treatment group and the intra-arterial treatment group showed no significant difference (P = 0.3707 and 0.3988, respectively). CONCLUSION: Both methods (intratumoral treatment and intraarterial treatment) showed a significantly good response rate and prolonged survival time compared with those of the control groups. However, no significant difference was found in the response rate or survival time between intratumoral treatment and intra-arterial treatment.

Monitoring the effect of anticoagulants on left atrial thrombi in patients with rheumatic heart disease: assessment with 111In-oxine-labelled platelet heart scintigraphy and transoesophageal echocardiography.

111In-oxine-labelled platelet heart scintigraphy (In-plt) was used to evaluate the activity of left atrial thrombi detected by transoesophageal echocardiography (TEE) in 16 cases of rheumatic heart disease. The effect of anticoagulants on the therapeutic intervention of these patients was evaluated by In-plt and TEE. In-plt was performed in all patients in serial pre- and post-anticoagulant therapy studies with anterior, 45 degrees left anterior oblique and left lateral views taken daily from the second to sixth day after injection of labelled platelets. After discontinuing anticoagulants for at least 1 week, only nine cases of left atrial thrombi were detected among the 16 cases by initial In-plt. After anticoagulants were again used for at least 3 weeks, all nine positive cases became negative on repeat In-plt. These results suggest that the diagnostic sensitivity of In-plt is lower than that of TEE. However, In-plt is more suitable and useful for evaluating the activity of left atrial thrombi after antithrombotic agent therapy and for monitoring the effect of anticoagulant therapy on left atrial thrombi in patients with rheumatic heart disease.

Technetium-99m tetrofosmin mammoscintigraphy findings related to the expression of P-glycoprotein mediated multidrug resistance.

We studied 30 patients with infiltrating ductal breast carcinomas to evaluate the relationship between the degree of accumulation of technetium-99m tetrofosmin (Tc-TETRO) and p-glycoprotein (Pgp) expression in breast tumor tissues. All of the 30 patients underwent Tc-TETRO mammoscintigraphy to calculate breast tumor uptake of Tc-TETRO to background (T/B) ratios before surgery or biopsy. Immunohistochemical analysis was performed to determine Pgp expression in the pathological specimens of the 30 breast tumors. The T/B ratios were significantly lower for tumors in 12 patients with positive Pgp expression (Group A) than for those in 18 patients with negative expression (Group B) (1.20 +/- 0.12 and 1.94 +/- 0.30, p < 0.05). Our results supported the opinion that Tc-TETRO mammoscintigraphy is helpful for determining in vivo the presence of multidrug resistance due to Pgp expression in breast carcinoma patients.

Expression of drug resistance protein related to Tc-99m MIBI breast imaging.

Adjuvant and neoadjuvant chemotherapy is increasingly being used in the treatment of breast cancer patients. However, drug resistance plays an important role in chemotherapy failure in this cancer. The aim of this study was to determine the correlation between technetium-99m sestamibi (Tc-99m MIBI) breast imaging results and expression of the drug resistance proteins (p-glycoprotein (Pgp), Ki-67 and mutant p53) in human breast cancer tissues. Twenty-four breast cancer patients underwent Tc-99m MIBI breast imaging before surgery or biopsy. Protein expression was investigated by immunohistochemical studies on multiple nonconsecutive sections of surgery or biopsy samples. Tumor to background (T/B) ratios calculated by Tc-99m MIBI breast imaging were correlated with protein expression determined by immunohistochemical studies. The T/B ratios were significantly lower in 8 patients with positive Pgp expression (Group 1) when compared with 16 patients with negative Pgp expression (Group 2) (1.40 +/- 0.11 and 2.76 +/- 0.60, p < 0.05). However, the differences of T/B ratios between the patients with positive and negative Ki-67 mutant p53 expression were not significant. Our data confirmed that Tc-99m MIBI breast imaging is useful for determination of the presence of Pgp expression in breast cancer patients. No significant relationship between Tc-99m MIBI breast imaging results and Ki67/mutant p53 was found.

Usefulness of technetium-99m tetrofosmin mammoscintigraphy as compared to mammography for detecting and differentiating palpable breast masses of young Taiwanese women.

Sixty young Taiwanese women with palpable breast masses detected by mammography and/or physical examinations underwent technetium-99m tetrofosmin (Tc-TETRO) mammoscintigraphy to assess its value for detecting and differentiating breast masses. The results showed that 42 of the 45 cases of breast carcinoma were detected by Tc-TETRO mammoscintigraphy. Fourteen of the 15 o benign breast lesions were differentiated by Tc-TETRO mammoscintigraphy. The diagnostic sensitivity, specificity, positive predictive value negative predictive value and accuracy of Tc-TETRO mammoscintigraphy were 93% 93% 98% 82% and 93% respectively. Thirty-eight of the 45 cases of breast carcinoma were detected by mammography. Twelve of the 15 of benign breast lesions were differentiated by mammography. The diagnostic sensitivity, specificity, positive predictive value, negative predictive value and accuracy of mammography were 84% 80% 93% 63% and 83% respectively. We concluded that Tc-TETRO mammoscintigraphy when compared to mammography significantly improves the accuracy of detection and differentiation of breast cancer in Taiwanese women.