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Activation of signal transducer and activator of transcription 3 in renal cell carcinoma: a study of incidence and its association with pathological features and clinical outcome.

PURPOSE: Signal transducer and activator of transcription 3 (STAT3) is known to have an important role in cytokine and growth factor signaling pathways. In various types of human malignant tumors STAT3 has been shown to be constitutively activated due to aberrant production of cytokines and growth factors. We examined the presence of STAT3 activation and its association with pathological features and clinical outcome in renal cell carcinoma cases. MATERIALS AND METHODS: We examined 48 paraffin embedded renal cell carcinoma specimens and corresponding nonneoplastic kidney tissues for the activation status of STAT3 on immunohistochemistry using anti-phospho-specific (p)-STAT3 antibody, which recognizes only activated STAT3. Based on the percent of cells with positive nuclear staining the activation status of STAT3 was determined and categorized into 2 groups, including low-less than 10% and high-90% or more tumor cells positive. The associations of the activation status of STAT3 with pathological features and clinical outcome were analyzed. RESULTS: Of 48 tumors 24 (50%) demonstrated high levels of nuclear immunostaining for p-STAT3, while the other 24 (50%) showed low levels. Adjacent nonneoplastic kidney tissues showed only little immunostaining for p-STAT3. A significant association of high levels of p-STAT3 with metastasis was observed (p = 0.0094). No significant associations of p-STAT3 immunostaining with pathological stage or grade were observed. A high level of p-STAT3 was a significant indicator of a poor prognosis on univariate and multivariate analysis (p = 0.0117 and 0.0439, respectively) CONCLUSIONS: Our results indicate a high frequency of STAT3 activation in renal cell carcinoma, especially in metastatic disease. STAT3 activation was an independent prognostic variable in renal cell carcinoma cases. Our results strongly suggest that the activation of STAT3 contributes to the development and progression of renal cell carcinoma.

Acute-Phase Proteins↗

Modulation of tamoxifen sensitivity by antisense Bcl-2 and trastuzumab in breast carcinoma cells.

BACKGROUND: Because the overexpression of HER-2 and Bcl-2 is associated with resistance to tamoxifen (TAM), the authors examined the effect of antisense (AS) Bcl-2 on sensitivity to TAM compared with the effect of trastuzumab on sensitivity to TAM in breast carcinoma cell lines. METHODS: Drug sensitivity was assessed in vitro using a [3-4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide assay with the breast carcinoma cell lines ZR-75-1, MDA-MB-453, and BT-474. AS Bcl-2 18-mer phosphorothioate oligonucleotide was applied. Apoptotic cell death was assessed with the terminal deoxynucleotidyl transferase-mediated biotinylated UTP nick-end labeling method, and gene expression was evaluated with Western blot analysis. RESULTS: The expression of Bcl-2 was identified in ZR-75-1 and BT-474 cells and, to a lesser extent, in MDA-MB-453 cells. Overexpression of HER-2 was identified in BT-474 cells, and moderate expression was identified in MDA-MB-453 and ZR-75-1 cells. Combination treatment with trastuzumab or AS Bcl-2 enhanced TAM sensitivity in ZR-75-1 cells, which showed 50% inhibitory concentration (IC50) values of 0.9 microM (7.2-fold increase) and 0.5 microM (13.0-fold), respectively. Combination treatment with trastuzumab or AS Bcl-2 slightly enhanced TAM sensitivity of BT-474 cells, with IC50 values of 3.0 microM (1.3-fold) and 1.5 microM (2.6-fold), respectively. The sensitivity of MDA-MB-453 cells to TAM was not enhanced by combination with trastuzumab or AS Bcl-2. Modulation of TAM sensitivity by AS Bcl-2 was superior to modulation by trastuzumab in HER-2-expressing and Bcl-2-expressing breast carcinoma cells. Enhanced sensitivity in combination with AS Bcl-2 was associated with down-regulation of Bcl-2 and pAkt, which was correlated with the induction of Bax and caspase-3, leading to apoptosis. CONCLUSIONS: AS Bcl-2 appeared to be superior to trastuzumab with respect to regulating the signal-transduction pathways involved in breast carcinoma cells.

Antibodies, Monoclonal↗

Autologous vein stent-graft: feasibility study.

PURPOSE: To evaluate expandable stents healed into vein wall as autologous vein stent-grafts for endoluminal grafting. MATERIALS AND METHODS: Balloon expandable stents were placed into external jugular veins of eight dogs. Stent and vein patency was followed by ultrasonography. Five weeks after stent placement, jugular veins with endothelialized stent were harvested. The autologous vein stent-grafts were divided into two groups. In group A, autologous vein stent-grafts (n = 3) were placed immediately into Baker solution for microscopic examination. In group B, autologous vein stent-grafts (n = 3) underwent mechanical manipulation; they were compressed, mounted on angioplasty balloon, pushed through a 9-F sheath and dilated. The autologous vein stent-graft endothelialization and changes after mechanical manipulation were evaluated by light and electron microscopy. RESULTS: Stent placement was successful in seven dogs. One stent migrated into the pulmonary artery. One well placed stent was damaged by compression dressing and thrombosed. At 5 weeks, gross and microscopic examinations revealed the autologous vein stent-grafts were fully covered by a 0.115- +/- 0.036-mm-thick neointimal layer. Small wall thrombus was observed in one autologous vein stent-graft. Repeated manipulations did not result in any intimal damage or stent loosening in the autologous vein stent-grafts. CONCLUSION: Expandable stents healed into a vein have potential to be used as autologous vein stent-grafts for endoluminal grafting without risk of disruption during percutaneous transcatheter introduction.

Animals↗

[Coronary risk factor management in primary practice in Shibuya, Tokyo].

OBJECTIVES: Many large-scale clinical trials have confirmed that coronary risk factors such as hypertension, hyperlipidemia and diabetes mellitus predict a higher incidence of cardiovascular events and that control of these risk factors reduces the incidence. However, the actual management of such risk factors and the resultant improvement of the cardiovascular events in primary practice remains unclear. The Heart Care Network Shibuya, a voluntary study group of regional primary physicians, surveyed the management of coronary risk factors and the clinical outcomes. METHODS: Behavioral patterns of the coronary risk factor was investigated in the management and resultant changes of the risk factors in 209 outpatients (mean age 65.6 +/- 11.2 years) with more than one of hypertension, hyperlipidemia, diabetes mellitus or prior myocardial infarction for 1 year. RESULTS: Prescriptions of anti-hypertensive (from 1.3 +/- 0.8 to 1.4 +/- 0.8 drugs per patient) and antihyperlipidemia drugs (from 0.70 +/- 0.4 to 0.73 +/- 0.4 drugs per patient) did not significantly increase. Patient education for diet (93% to 97%, p = 0.077), exercise (69% to 81%, p < 0.05) and nonsmoking (66% to 86%, p < 0.05) significantly increased after 1 year. Blood pressure decreased from 142 +/- 16/81 +/- 10 to 138 +/- 78/78 +/- 9 mmHg (p < 0.05), serum total cholesterol level decreased from 215 +/- 39 to 203 +/- 39 mg/dl (p < 0.05). As a result, more patients attained the treatment goals recommended in the guidelines by the Japanese Society of Hypertension (34.6% to 46.8%) and Japan Atherosclerosis Society (40.2% to 49.5%), respectively. However, none of blood hemoglobin A1c level, body mass index or smokers significantly changed. CONCLUSIONS: Regional practitioners attempted to control all coronary risk factors. Hypertension and hyperlipidemia, which are relatively more dependent on the medical management, improved. In contrast, diabetes mellitus, obesity or smoking, which require life style changes, did not improve. The main issue in the risk factor management is how physicians act rather than specific actions.

Aged↗

Pharmacokinetic differences between Caucasian and Japanese subjects after single and multiple doses of a potential combined oral contraceptive (Org 30659 and EE).

OBJECTIVES: To compare the pharmacokinetic parameters and safety of the progestagen, Org 30659, (17alpha)-17-hydroxy-11-methylene-19-norpregna-4,15-dien-20-yn-3-one), and ethinyl estradiol (EE) in Caucasian and Japanese women after single and multiple doses. METHODS: This was an open-label parallel design of a single dose followed by a multiple dose period in healthy young Japanese and Caucasian subjects. RESULTS: The area under the curve (AUC) of Org 30659 after single dosing was increased by a factor of 1.75 [90% confidence interval (CI): 1.48-2.08] in Japanese women compared to Caucasian women. At steady state, this difference increased to a factor of 1.90 (90% CI: 1.60-2.25). The AUC of EE after single dosing was similar in Caucasian and Japanese women, but at steady state it was increased by a factor 1.38 (90% CI: 1.15-1.64) in the Japanese group. Weight normalization reduced, but did not remove, all the observed differences. Sex hormone binding globulin played no significant role in the differences between Caucasian and Japanese subjects. Both the single- and multiple-dose treatments with Org 30659/EE were generally well tolerated by all subjects. The Japanese population reported more and different treatment-related adverse events than the Caucasian population. CONCLUSIONS: The peak concentration and extent of exposure of Org 30659, and to a lesser extent of EE, in Japanese women are higher than in Caucasian women. Furthermore, the peak concentration and extent of exposure at steady state of Org 30659, and to a lesser extent of EE, are higher than would be predicted assuming linear pharmacokinetics over time. No major safety issues were observed.

Adult↗

Experimental small bowel transplantation using newborn intestine in rats: III. Long-term cryopreservation of rat newborn intestine.

BACKGROUND: If long-term organ cryopreservation can be attained, a significant achievement will have been made to address the problem for donor shortage. Fetal intestine has been known to revascularize naturally without vascular anastmosis. The authors have confirmed previously that the newborn intestine also could develop to maturity in the host omentum. Here, the authors examined whether the cryopreserved newborn intestine could revascularize in the syngeneic combination using the 2 different solutions and whether cryopreservation affect their antigenicity in the allogeneic combination. METHODS: Inbred rat strains of LEW (MHC haplotype; RT1(l)) and BN (RT1(n)) were used. LEW newborn intestinal grafts were stored in RPMI-1640 or University of Wisconsin solution with 10% DEMSO (n = 10 in each group). The grafts were placed into a cold (4 degrees C) preservation solution for 30 minutes and then placed into a freezing chamber and cooled to -80 degrees C at -1 degrees C/min after 12 hours quenched to -180 degrees C in liquid nitrogen for longer than 30 days. Then, the cryopreserved grafts under the 2 different solutions were transplanted syngenicaly (LEW to LEW). The cryopreserved BN grafts also were implanted into the LEW omentum pouch. The allotransplantation was received with a 14-day high-dose course of tacrolimus (0.64 mg/kg, intramuscularly). The grafts were evaluated histologically at 4 weeks after transplantation. Fresh newborn intestines implanted in this syngeneic and allogeneic combination were evaluated as each control group. RESULT: In the syngeneic combination, more than 90% of the mature intestine were obtained. There was no significant difference among the different solution and the fresh group. However, in the allogeneic combination, both fresh and cryopreserved grafts were histologically poor. CONCLUSIONS: This is the first report showing that long-term cryopreservation was not harmful for neovascularization of newborn intestine. Long-term cryopreservation did not reduce the antigenicity of the newborn intestine. J Pediatr Surg 36:602-604.

Animals↗

Differences in the relationship between BMI and percentage body fat between Japanese and Australian-Caucasian young men.

This cross-sectional study aimed to determine ethnic and environmental influences on the relationship between BMI and percentage body fat, using a sample of 144 Japanese and 140 Australian-Caucasian men living in Australia, and eighty-eight Japanese men living in Japan. Body composition was assessed by anthropometry using standard international methods (International Society for the Advancement of Kinanthropometry protocol). Body density was predicted using Durnin and Womersley's (1974) equation, and percentage body fat was calculated from Siri's (1961) equation. Significant (P<0.05) ethnic differences in stature, body mass and BMI were observed between Japanese and Australian men, but no ethnic differences were observed in their percentage body fat and height-corrected sum of skinfold thicknesses. No differences were found in the BMI-percentage body fat relationship between the Japanese subjects living in Australia and in Japan. Significant (P<0.05) ethnic differences in the BMI-percentage body fat relationship observed from a comparison between pooled Japanese men (aged 18-40 years, BMI range 16.6-32.8 kg/m2) and Australians (aged 18-39 years, BMI range 16.1-31.4 kg/m2) suggest that Japanese men are likely to have a greater percentage body fat than Australian men at any given BMI value. From the analyses, the Japanese men were estimated to have an equivalent amount of body fat to the Australian men at BMI values that were about 1.5 units lower than those of the Australians (23.5 kg/m2 and 28.2 kg/m2, respectively). It was concluded that Japanese men have greater body fat deposition than Australian-Caucasians at the same BMI value. Japanese men may therefore require lower BMI cut-off points to identify obese individuals compared with Australian-Caucasian men.

Adipose Tissue↗

[Production and clinical application of fibrin sealant with high concentrated fibrin (fibrin patch)].

OBJECT: The sealing properties of fibrin sealant with high concentrated fibrin (fibrin patch) were examined. MATERIAL AND METHODS: A commercial fibrin sealant (Bolheal) produced from pooled human plasma was utilized for this study. The fibrin sealant made of fibrinogen and thrombin solutions mixed in a volume ratio 5:1 was applied as the fibrin sealant with high concentrated fibrin (fibrin patch). The burst pressure of the fibrin clots of either 1:1 or 5:1 mixing ratio, which sealed the small holes, was measured by a water-leak preventing model. The tensile strength of the fibrin patch was measured by the breaking pressure of the fibrin clot. The burst pressure of the fibrin patch, which sealed the dural defect with a diameter of 15 mm, was compared with that of expanded polytetrafluoroethylene (ePTFE). RESULTS: The burst pressure was elevated from 287 +/- 23.1 to 445 +/- 30.5 mmHg by changing the mixing ratio from 1:1 to 5:1. The breaking pressure of the fibrin patch showed 131 +/- 25.4 mmHg and that of the patch mixed at the ratio of 1:1 showed 46.6 +/- 9.9 mmHg. The result of dural repair with the fibrin patch revealed higher sealing effectiveness than that of ePTFE. The burst pressure averaged 70.5 +/- 21.4 mmHg in the fibrin patch samples and 51.4 +/- 13 mmHg in the ePTFE samples. CONCLUSION: The fibrin patch revealed higher performance as a sealant and has the potential to be a candidate for acceptance as the new dural repair material.

Brain↗

Memory, attention, and executive functions before and after sine and pulse wave electroconvulsive therapies for treatment-resistant major depression.

OBJECTIVE: Studies of the cognitive effects of electroconvulsive therapy (ECT) have resulted in controversial findings up to now, partly because researchers and reviewers have not always made a clear distinction among various aspects of cognition and because there are many parameters involved in the administration of ECT that have a potential impact on cognition. The present study focused on the impact of sine and pulse waveforms on anterograde memory and nonmemory cognitive functions. METHODS: We assigned 18 patients with unipolar major depression or bipolar I or II disorder, most recent episode depressed, to receive sine wave or pulse wave ECT and assessed their cognitive function before and after ECT, using a neuropsychologic test battery that measured anterograde memory, attention, and executive functions. Outcomes were measured, on average, 8.2 days after the last ECT session. RESULTS: Both waveforms were equally effective in alleviating depression. Those who received sine wave ECT showed statistically significant deterioration in attention and executive tasks, such as the Stroop test, which measures selective attention (P = 0.02), and the dual task, which taps divided attention (P = 0.01). On the other hand, those who received pulse wave ECT improved to a significant degree in certain memory tasks, such as visual memory (P = 0.01) and general memory (P = 0.01) of the Wechsler Memory Scale-Revised (WMS-R), as well as in the dual task (P = 0.01). The between-group comparison revealed robust superiority of the pulse wave over the sine wave in terms of the dual task (P = 0.004). CONCLUSIONS: Anterograde memory improved to a statistically significant or nonsignificant degree at 1 week post-ECT in comparison with pre-ECT regardless of waveforms. Attention/executive functions tended to deteriorate with sine wave ECT but improved with pulse wave ECT.

Attention↗

Metal concentrations in the serum and hair of patients with titanium alloy spinal implants.

STUDY DESIGN: A retrospective study of serum and hair metal concentrations in patients with titanium alloy spinal implants was performed. OBJECTIVE: To determine the incidence and possible causes of abnormal metal concentrations. SUMMARY OF BACKGROUND DATA: Several studies have demonstrated that metal debris are present in the tissues surrounding titanium alloy spinal implants. However, few studies suggest that metals dissolve, circulate in the body fluid, and accumulate in remote organs. METHODS: Titanium, aluminum, and vanadium concentrations in serum and hair were measured after surgery in 46 patients with titanium alloy spinal implants (12 patients in the implant failure group and 34 patients in the no implant failure group) and 20 patients without spinal implants (control group). All the subjects were examined again 1 year after the first examination or implant removal. RESULTS: Of the 46 patients with titanium alloy spinal implants, 16 patients (34.8%) exhibited abnormal serum metal concentrations and 11 patients (23.9%) exhibited abnormal hair metal concentrations. In the control group, three patients (15%) exhibited only abnormal serum and metal aluminum concentrations at the first examination. In both of the two patients who exhibited abnormal serum titanium concentrations and then had their spinal implants removed, the serum and hair titanium levels decreased to beneath the reference value limit in 1 year after the removal. Comparison of the implant failure and no implant failure groups showed no significant differences in the incidence of abnormal serum concentrations of titanium, aluminum, or both metals. Therefore, serum metal concentrations did not seem to be a useful indicator of hardware loosening or implant failure. CONCLUSIONS: Approximately one third of patients with titanium alloy spinal implants exhibited abnormal serum or hair metal concentrations at a mean time of mean 5.1 years after surgery. Titanium or aluminum may travel to distant organs after dissolution of metals from the spinal implants.

Adolescent↗

A new noninvasive measurement system for wave intensity: evaluation of carotid arterial wave intensity and reproducibility.

Wave intensity (WI) is a new hemodynamic index that provides information about the dynamic behavior of the heart and the vascular system and their interaction. Carotid arterial wave intensity in normal subjects has two positive peaks. The first peak, W(1), occurs during early systole, the magnitude of which increases with increases in cardiac contractility. The second peak, W(2), which occurs towards the end of ejection, is related to the ability of the left ventricle to actively stop aortic blood flow. Between the two positive peaks, a negative area, NA, is often observed, which signifies reflections from the cerebral circulation. The time interval between the R-wave of ECG and the first peak (R - W(1)) corresponds to the pre-ejection period, and that between the first and second peaks (W(1) - W(2)) corresponds to ejection time. We developed a new ultrasonic on-line system for obtaining WI and arterial stiffness (beta). The purpose of this study was (1) to report normal values of various indices derived from WI and beta measured with this system, and (2) to evaluate the intraobserver and interobserver reproducibility of the measurements. The measurement system is composed of a computer, a WI unit, and an ultrasonic machine. The WI unit gives the instantaneous change in diameter of the artery and the instantaneous mean blood velocity through the sampling gate. Using these parameters and blood pressure measured with a cuff-type manometer, the computer gives WI and beta. We applied this method to the carotid artery in 135 normal subjects. The mean values of W(1), W(2), NA, R - W(1), and W(1) - W(2) were 8 940 +/- 3 790 mmHg m/s(3), 1 840 +/- 880 mmHg m/s(3), 27 +/- 13 mmHg m/s(2), 104 +/- 14 ms, and 270 +/- 19 ms, respectively. These values did not show a significant correlation with age. The mean value of beta was 10.4 +/- 4.8 and the values significantly correlated with age (men: r = 0.66, P < 0.0001; women: r= 0.81, P < 0.0001). The reproducibility was evaluated by intraobserver intrasession (IA), intraobserver intersession (IE), and interobserver intrasession variability (IO). The reproducibility of R - W(1) and W(1) - W(2) was high: the mean coefficient of variation (mCV) of IA was less than 3%; 95% confidence limits from the mean values (CL) were less than 8% for IE and less than 4% for IO. The reproducibility of W(1) and beta was good: mCV for IA was less than 10%; CL for IE and IO were less than 17%. W(2) and NA showed a higher variability than other indices: mCV for IA was less than 13%, and CL for IE and IO were less than 36%. However, two sessions by the same observer and two sessions by different observers were not biased. Wave intensity measurements with this system are clinically acceptable.

Adult↗

Quantification of retinal nerve fiber defects in glaucoma: three-dimensional analysis by Heidelberg retina tomograph.

PURPOSE: To describe a new method of quantifying retinal nerve fiber layer defects (NFLD) in glaucomatous eyes using the Heidelberg Retina Tomograph (HRT). METHODS: Mean tomographic images including the optic disc and peripapillary area were constructed using HRT. An image field of 15 degrees x 15 degrees or 20 degrees x 20 degrees was used for the NFLD analysis. Data on the nerve fiber layer thickness was collected and further analyzed circumferentially across the NFLD at a position 500 microm away from the optic disc margin. We studied 31 patients with early to moderate open-angle glaucoma, ie, with visual field defects appearing earlier than stage 3 of the modified Aulhorn-Greve classification. We determined the width (W), maximum depth (D), and cross-sectional area of the NFLD (A), and we identified correlations between these parameters and the visual field indices from Humphrey Visual Field tests, mean deviation (MD) and corrected pattern standard deviation (CPSD). RESULTS: NFLD parameters could be obtained from 20 of 31 eyes (65%). There was a statistically significant correlation between the D and A parameters, and between these parameters and the maximum depression threshold in the corresponding visual field. No significant correlation was found between the NFLD parameters, the global visual field indices (MD, CPSD) and the mean value of the total deviation (TD) in the corresponding hemifield visual field. CONCLUSIONS: A cross-sectional NFLD image can be obtained using HRT. Among the three NFLD parameters, maximum depth (D), and area under the surface (A) correlated well with the visual field threshold.

Diagnostic Techniques, Ophthalmological↗

A novel 18-amino acid deletion in apolipoprotein E associated with lipoprotein glomerulopathy.

BACKGROUND: Lipoprotein glomerulopathy (LPG) is a novel disease characterized by proteinuria, lipoprotein thrombi in glomeruli, and an increased concentration of plasma apolipoprotein (apo) E. Previous studies have shown that a genetic disorder of apo E may be associated with the genesis of this disease. METHODS: An apo E mutation was analyzed in a 57-year-old Japanese male with LPG and systemic atherosclerotic complications. Apo E phenotypes were analyzed by isoelectric focusing and immunoblotting. Apo E genotypes were determined by restriction fragment isotyping with HhaI. Polymerase chain reaction (PCR) products of apo E coding region exons 3 and 4 were cloned into pT7Blue-T-vector and were sequenced. RESULTS: A novel apo E mutation was identified in this patient and his family. There was a discrepancy between an apo E phenotype (E1/3) and genotype (E3/3). Sequence analysis showed a 54 bp deletion in exon 4 of the apo E gene, causing the 18-amino acid deletion (Gln 156-Gly 173-->0). This deletion mutation was further confirmed by the detection of a short fragment of PCR-amplified DNA using polyacrylamide gel electrophoresis. The patient was a heterozygote with apo E1, and this mutation was determined to be the structural basis for the apo E1 phenotype. One of two daughters was a heterozygous carrier of apo E1, although she did not have proteinuria or atherosclerotic diseases. CONCLUSIONS: Apo E1 (Gln 156-Gly 173-->0) is a novel mutation of apo E that may be etiologically related to LPG and to the development of atherosclerosis. The result of this family study suggests that the occurrence of LPG may involve other genetic or environmental factors.

Adult↗

Diagnostic value of FDG PET and salivary gland scintigraphy for parotid tumors.

PURPOSE: The purpose of this study was to examine the diagnostic value of the combination of F-18 fluorodeoxyglucose (FDG) PET and Tc-99m pertechnetate salivary gland scintigraphy in parotid tumors. MATERIALS AND METHODS: Seventy-two patients with benign parotid gland tumors (n = 52), malignant parotid tumors (n = 12), and inflammation (n = 8) underwent both FDG PET and salivary gland scintigraphy within 1 week, and 66 of the patients also underwent gallium scintigraphy. All patients were negative on their first fine-needle aspiration (FNA). RESULTS: Malignant parotid tumors showed significantly higher FDG uptake (standard uptake values [SUVs]) than both benign tumors and inflammation, except in Warthin's tumor (5.82 +/- 3.95 vs. 2.07 +/- 1.33; P <0.01). Although the SUV values of Warthin's tumor and malignant parotid tumors overlapped somewhat, Warthin's tumor did demonstrate increased radiotracer uptake, and it was reliably distinguished from other parotid gland tumors by the use of salivary gland scintigraphy. Considering a SUV value >3 as being positive for malignancy and excluding Warthin's tumor on the basis of salivary gland scintigraphy, sensitivity and specificity of FDG PET were 75% and 80%, respectively. These results were superior to those of gallium scintigraphy (58% and 72%, respectively). CONCLUSIONS: Although the diagnostic value of FDG PET in the differentiation of malignant from benign parotid gland tumors was limited because of the high FDG uptake in some benign tumors, and particularly pleomorphic adenomas, combining salivary gland scintigraphy with FDG PET may help to negate this drawback, and this combination may be a more promising approach for differentiation of various parotid gland tumors in patients compared with nondiagnostic needle aspiration.

Adolescent↗

Treatment with anti-TGF-beta antibody ameliorates chronic progressive nephritis by inhibiting Smad/TGF-beta signaling.

BACKGROUND: Although short-term treatment with anti-transforming growth factor-beta (TGF-beta) antibody (alphaT) has been shown to prevent early glomerular lesions, its long-term effects and molecular mechanisms, including intracellular signaling, remain poorly understood. We examined whether alphaT treatment induces prevention of renal insufficiency and fibrosis, and affects the TGF-beta/Smad signaling pathway in rats with chronic progressive anti-thymocyte serum (ATS) nephritis induced by repeated ATS injections on days 0 and 7. METHODS: Nephritic and non-nephritic rats were treated with either alphaT or control immunoglobulin (Ig)G twice weekly for 4 weeks from days 7 to 35 (each group, N= 21). Renal lesions and cortical expression of TGF-beta1, TGF-beta2, TGF-beta3, type II TGF-beta receptor (TbetaRII), Smads, type I collagen, and plasminogen activator inhibitor-1 were examined by immunohistochemistry, Western blot, and/or real-time reverse transcription polymerase chain reaction (RT-PCR). The binding of Smad3 in renal cortical cell nuclei to the Smad-binding element (SBE) was investigated by the electrophoretic mobility shift assay. RESULTS: Nephritic rats developed heavy proteinuria, renal insufficiency, and increased extracellular matrix deposition resulting in renal fibrosis. Cortical expression levels of TGF-beta1, TGF-beta2, TbetaRII, and Smad2, but not TGF-beta3, Smad3, and Smad4 were increased. Expression and preferential localization of phosphorylated Smad2/3 in the glomerular and tubular cell nuclei, and Smad3-SBE complex-forming activity were also increased. Four-week alphaT treatment resulted in marked amelioration of chronic progressive ATS nephritis at 8 weeks. CONCLUSION: In chronic progressive ATS nephritis, the TGF-beta/Smad signaling was up-regulated. TGF-beta blockade by alphaT suppressed the progression of renal scarring, at least in part, via inhibition of activated TGF-beta/Smad signaling.

Animals↗

Anterior expandable strut cage replacement for osteoporotic thoracolumbar vertebral collapse.

OBJECT: The authors investigated the usefulness of using an expandable cage strut in anterior reconstruction after osteoporotic vertebral collapse in patients with neurological deficits. METHODS: Twenty-eight patients who had undergone expandable cage strut-augmented anterior thoracolumbar reconstruction participated in a follow-up review for a mean of 4.9 years. Radiographs were reviewed for kyphosis, lateral tilt of the implant, cage subsidence, the presence of a solid fusion mass, and instrumentation failure. Changes in neurological status and visual analog scale (VAS) pain score, as well as technique-related complications, were examined. The mean angles +/- the standard deviations of kyphosis correction 4 to 6 weeks after surgery and at final follow-up examination were 10.4 +/- 7.6 degrees and 5.6 +/- 6.0 degrees, respectively. The mean subsidence of the expandable cage within the adjacent vertebrae was 2.5 +/- 3.0 mm at the final follow-up examination. Neurological improvement at the final follow up was more significant in patients with Type I (wedge-type) than Type 2 (flat-type) (p = 0.037) or Type 3 (concave-type) (p = 0.006) vertebral collapse. Follow-up VAS scores were significantly higher in patients with Type 1 than Type 3 collapse (p = 0.012). In all cases the authors observed solid union with incorporation of the cage. There were no surgery-related complications. CONCLUSIONS: An expandable titanium cage strut seems useful in vertebral body replacement in patients with osteoporotic thoracolumbar collapse. Favorable results were obtained in cases of Type I collapse (wedge type) in which the middle and posterior columns remained comparatively intact.

Aged↗

[A study of recurrent pancreatic cancer with metastatic liver tumors after pancreatectomy].

BACKGROUND: Pancreatectomy is the best treatment for pancreatic cancer. However, there is a high risk of post-operative complications, such as local recurrence, metastatic lymphadenopathy, carcinomatosa peritonitis and liver metastasis. Presently, there is no significant treatment that has yet had a strong impact on recurrent pancreatic cancer. This study was conducted concerning recurrent pancreatic cancer with metastatic liver tumors after pancreatectomy. SUBJECTS AND METHODS: Between April 1998 and March 2005, our institute treated recurrent pancreatic cancer patients with liver metastasis. This study consisted of groups who received therapy and those who did not, and their subsequent survival rate was also studied. RESULTS: Nine cases had a recurrent pancreatic cancer with metastatic liver tumors. According to the treatment modality, the study population was classified into two groups: one group consisted of 4 patients with no treatment and the other group consisted of 5 patients who received treatment with gemcitabine (GEM). The mean survival rate for the group who received no treatment was 6.6 months. The mean survival rate for the group who received the treatment was 22.3 months. In addition, one year survival rate for those who received no treatment was 0%. The one year survival rate for those who received the treatment was 75%. The group with treatment showed better results in overall mean survival rates, as well as a higher one-year survival rate than the group with no treatment. The GEM administration included both intraarterial infusion and intravenous infusion. CONCLUSIONS: Prolongation of the survival period was obtained by administration of GEM for recurrent pancreatic cancer with metastatic liver tumors and inoperable advanced pancreatic cancer. We attempted to utilize the active treatment for recurrent pancreatic cancer with metastatic liver tumors. Thus, it was indicated that the therapy can be effective against recurrent pancreatic cancer with metastatic liver tumors.

Aged↗

Dose and load studies for subcutaneous and oral delivery of poly(lactide-co-glycolide) microspheres containing ovalbumin.

Poly(lactide-co-glycolide) microspheres containing different loads of OVA (0.05, 0.1, 0.5 and 1.0% w/w) were manufactured by a w/o/w emulsion/solvent evaporation method. Low load efficiencies of less than 20% were observed. Normal size distributions with mean volume diameters ranging from 3.7 to 4.7 microns were obtained for different batches. The in vitro release of OVA from different loaded microspheres showed an expected burst release with all batches. The in vivo dose study (1, 10, 25, 50 micrograms of OVA) was performed by subcutaneous and oral inoculation in mice by single (0 week) or double (0 and 3 weeks) administration of PLGA 50/50 microspheres containing 0.1% OVA. Subcutaneous administration showed an immune response (serum Ig levels by ELISA) statistically (Fisher's paired t-test; P < 0.05) above OVA saline negative controls at 3, 6 and 12 weeks after administration. Oral administration of microspheres produced statistically higher systemic immune responses at the higher doses. Single and double inoculation orally and subcutaneously produced similar serum antibody levels. The in vivo load study was performed by subcutaneous and oral administration to mice of 25 micrograms OVA contained in various loaded (0.05, 0.1, 0.5 and 1.0% w/w) microspheres. Serum immune responses at 3, 6, and 12 weeks after inoculation were statistically above OVA saline controls and were inversely proportional to the OVA load using either route. This observation suggested a relationship between the number of microspheres delivered and the in vivo serum response. Single subcutaneous administration of 0.05 or 0.1% OVA loaded PLGA 50/50 microspheres induced larger immune responses compared with complete Freund's adjuvant.

Administration, Oral↗