Detrusor instability with equivocal obstruction: A predictor of unfavorable symptomatic outcomes after transurethral prostatectomy

AIMS: To elucidate whether preoperative urodynamic findings can predict outcomes of transurethral resection of the prostate (TUR-P). METHODS: Sixty-two patients with symptomatic benign prostatic hyperplasia were categorized in three different ways based on findings of preoperative pressure-flow study (PFS) and cystometry: urodynamic obstruction (determined by the Abrams-Griffiths nomogram), detrusor instability (DI), and combination of both. Outcomes of TUR-P regarding symptom, function, and quality of life (QOL) were analyzed by changes in the International Prostate Symptom Score (I-PSS), maximum flow rate in uroflowmetry, and QOL index before and after TUR-P, respectively. Overall outcome was defined as success when all of the three categories showed successful improvement. RESULTS: Neither urodynamic obstruction alone nor DI alone predicted outcomes of TUR-P. However, symptomatic and overall outcomes were significantly worse in patients who were not obstructed but had DI. Postoperative persistent DI was more frequently noted in patients without clear obstruction (60%) than in those with obstruction (27%). Patients with equivocal obstruction showed less satisfactory symptomatic outcomes of TUR-P when DI was accompanied. Persistent DI might be the principle cause of unfavorable outcomes. CONCLUSIONS: Preoperative evaluation of DI is of benefit because it enhances predictive value of the PFS.     

PPARgamma activation and adipocyte differentiation induced by AS-6, a prenyl-phenol antidiabetic antibiotic

The prenyl-phenol antibiotics ascochlorin-related compounds, are known to reduce serum cholesterol and triglyceride, suppress hypertension, and ameliorate types-I and II diabetes. However, little is known about the molecular mechanism for these physiological effects. Here we report that the ascochlorin derivative, 4-O-carboxymethyl ascochlorin (AS-6) acts as a potent activator of the nuclear hormone receptor, PPARgamma, although it does not activate the related receptors, PPARalpha, PPARdelta or RARalpha. AS-6 interacts directly with the PPARgamma molecule in vitro, and induces differentiation of the mouse preadipocyte cell line 3T3-L1. Our results suggest that AS-6 is a partial agonist for PPARgamma with a novel chemical structure.     

Changes in the leukocyte distribution and surface expression of adhesion molecules induced by hypothalamic stimulation in the cat

Emotions and the neuroendocrine system are known to affect leukocyte distribution. However, there have so far been few reports on the relationship between hypothalamically induced emotional behavior and the endocrine-immune response. We previously reported changes in the leukocyte distribution and adhesion molecules induced by anteromedial hypothalamus stimulation (AH stimulation), which elicits restlessness behaviors in the cat. In this study, we examined ventromedial hypothalamus stimulation (VMH stimulation), which elicits threat behaviors. In addition, the endocrine responses after VMH stimulation were evaluated. VMH stimulation as well as AH stimulation induced elevations of plasma cortisol and epinephrine levels and granulocytosis and lymphopenia. In contrast, VMH stimulation induced only an elevation of plasma norepinephrine and elicited an opposite pattern of CD62L expression on the leukocyte subpopulations. The different endocrine-immunological reactions between VMH stimulation and AH stimulation were thus associated with different types of behavioral responses.     

Detection of hypervascular hepatocellular carcinoma by dynamic magnetic resonance imaging with double-echo chemical shift in-phase and opposed-phase gradient echo technique: comparison with dynamic helical computed tomography imaging with double arterial phase

PURPOSE: The technique of double-echo chemical shift gradient echo magnetic resonance imaging (MRI) with the fast low-angle shot (double-echo FLASH) sequence provides in-phase and opposed-phase images in a single breath hold. The purpose of this study was to evaluate the efficacy of dynamic MRI with double-echo FLASH imaging for the detection of hypervascular hepatocellular carcinoma by comparing it with dynamic helical computed tomography (CT) imaging with double arterial phase. MATERIALS AND METHODS: Twenty-nine patients with 67 hypervascular hepatocellular carcinoma nodules who underwent both dynamic MRI with double-echo FLASH imaging (repetition time/echo time/flip angle: 160/3.6, 7.0/80 degrees ) and dynamic helical CT imaging with double arterial phase were enrolled in the study. For dynamic MRI, precontrast, arterial, portal venous, and equilibrium phase images were obtained before and approximately 19, 60, and 120 seconds, respectively, after intravenous injection of 0.1 mmol/kg of gadopentetate dimeglumine at a rate of 2 ml/s. For dynamic CT imaging, quadraphase images, including early arterial, late arterial, portal venous, and equilibrium phases, were obtained serially approximately 20, 30, 70, and 180 seconds, respectively, after intravenous administration of 2 ml/kg of 300 mgI/ml of nonionic contrast medium at a rate of 5 ml/s. Three masked observers independently interpreted images obtained with each technique in random order, separately and without patient identifiers. Sensitivity and positive predictive values as well as the area below the alternative-free response receiver operating characteristic curve (Az) for each imaging technique were calculated and compared statistically. RESULTS: Mean sensitivity and positive predictive values of MRI for hypervascular hepatocellular carcinoma were 48% and 94%, respectively, and those of CT imaging were 47% and 91%, respectively. In 11 (38%) of the 29 patients, at least one observer judged dynamic MRI to be superior, whereas in 5 patients (17%), dynamic CT was judged to be superior. There was no significant difference in the sensitivity and positive predictive values between these techniques (p > 0.05). There was no significant difference either in mean Az values between CT (0.55) and MRI (0.57) (p = 0.61). CONCLUSION: Dynamic MRI with double-echo FLASH imaging can detect hypervascular hepatocellular carcinoma as well as dynamic helical CT imaging with double arterial phase.     

High dose rate endovascular brachytherapy in aorto-iliac lesion for the prevention of restenosis

This study examined the applicability of endovascular brachytherapy to larger del arteries such as the abdominal aorta and iliac artery. Endovascular brachytherapy using an Ir-192 HDR source was administered 11 times to nine patients who had undergone percutaneous transluminal angioplasty (PTA) between 1995 and 1999. The follow-up lasted 13 to 55 months after treatment (median, 24 months). Eight of the 11 lesions have been controlled so far. Although one case developed thrombus inside the stent five months later, recanalization was achieved by means of retreatment. One patient who underwent low-dose irradiation (6 Gy) without stent implantation showed restenosis five months after treatment. We used a centering catheter that did not block the blood stream for exact centering of the radiation source in larger vessels such as the abdominal aorta. Although endovascular brachytherapy is a promising and safe procedure, careful follow-up is needed to detect untoward reactions such as thrombosis.     

N-Myc induction stimulated by insulin-like growth factor I through mitogen-activated protein kinase signaling pathway in human neuroblastoma cells

Insulin-like growth factor I (IGF-I) stimulates proliferation, survival, and differentiation in many cell types, including pediatric neuroblastomas. The effect is mediated via the type I IGF-I receptor (IGF-IR), which is essential for growth in these cells. Several lines of evidence indicate that IGF-IR function may be particularly important in the pathogenesis of neuroblastoma. Amplification of the N-myc oncogene or overexpression of N-Myc oncoprotein has been reported to be associated with resistance to therapy and poor prognosis of neuroblastomas. It was therefore of interest to analyze whether IGF-I signaling regulated expression of N-myc in KP-N-RT human neuroblastoma cells as an experimental model that has amplified N-myc. We found that IGF-I induces N-myc mRNA and protein in the KP-N-RT with maximums of four and six times more than the basal level at 2 and 3 h after stimulation, respectively. These effects of IGF-I were blocked by a neutralizing antibody against IGF-IR (alpha-IR3). Exogenous IGF-I induced phosphorylation and activation of extracellular signal-regulated kinases p44/42 (ERK1 and ERK2), with a maximal level 30 min after the stimulation. The MEK1 inhibitor PD98059 reduced IGF-I-mediated p44/42 MAPKs phosphorylation and produced a parallel reduction of IGF-I-stimulated N-Myc induction. Furthermore, both alpha-IR3 and PD98059 inhibited G1-S cell cycle progression stimulated by IGF-I. Our results demonstrate that IGF-I induces N-Myc in the KP-N-RT neuroblastoma cell line at the RNA level and establishes a clear correlation between N-Myc induction and activation of p44/42 MAPK signaling.     

New Hepatocellular Carcinoma Cell Line SUHC-1 Established from a Patient with Hepatitis C Virus RNA in Serum

A new human hepatocellular carcinoma cell (HCC) line, designated SUHC-1, was derived from a Japanese patient with hepatocellular carcinoma having antibody to hepatitis C virus (HCV) and HCV-RNA in his serum, and established in tissue culture. This cell line exhibited typical epithelial cell morphology in culture as observed by phase-contrast and electron microscopy. The SUHC-1 cells produced albumin and α₂-macroglobulin. Chromosomal analysis showed several rearrangements at short and long arms of chromosome 1, 17 and 20 (1p–, 1q–, i(1q), i(17q) and 20q +) with a modal number of 91. HCV-RNA was not detected in the supernatant of SUHC-1 cells by nested polymerase chain reaction assay or in the SUHC-1 cells by the in situ hybridization method. We concluded that complete HCV does not exist in the SUHC-1 cell line. The SUHC-1 cell line is the first line of HCC to have been derived from a patient with persistent HCV infection, and may provide a suitable model for studies of hepatocarcinogenesis related to HCV.     

Angiotensin blockade inhibits osteopontin expression in non-infarcted myocardium after myocardial infarction

Osteopontin has been reported to have an important role in cardiac fibrosis. However, little is known about the effects of angiotensin-converting enzyme inhibitor (ACEI) and angiotensin type 1 receptor blockers (ARB) on osteopontin expression in infarcted myocardium. The purpose of this study was to elucidate the effects of an ACEI (perindpril) and an ARB (candesartan cilexitil) on cardiac function as assessed by Doppler echocardiography and cardiac osteopontin expression associated with cardiac remodeling in myocardial infarcted rats. ACEI or ARB was administered after myocardial infarction (MI). At 4 weeks after MI, cardiac function, and mRNAs in non-infarcted myocardium were analyzed. ACEI and ARB equally prevented left ventricular dilatation, reduction of ejection fraction, and the increase in E/A wave velocity ratio and the rate of E wave deceleration by MI. ACEI and ARB significantly suppressed increased mRNA expression of atrial natriuretic peptide, brain natriuretic peptide, osteopontin, and collagen I and III in the non-infarcted ventricle at 4 weeks. Immunohistochemically stained osteopontin was increased in interstitial fibrosis of non-infarcted myocardium. Both ACEI and ARB significantly prevented cardiac fibrosis and osteopontin expression. In conclusion, angiotensin blockade inhibits osteopontin expression in non-infarcted myocardium and prevents cardiac remodeling after MI.