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PubMed2006

The role of apoptotic or nonapoptotic cell death in determining cellular response to anticancer treatment.

AIMS: Apoptosis, an early response cell death, is a useful marker for predicting tumour response after anticancer treatment; however, late-response cell death or nonapoptotic cell death, autophagy, can also be observed. This article reviews a rational model for predicting tumour response by assessing the influence of nonapoptotic cell death, and thereby developing a more efficient strategy for enhancing the therapeutic effect of anticancer treatment. METHOD: Literature search of clinical and experimental studies on "cell death and cancer" using established databases, including PUBMED. FINDINGS: Although induction of apoptosis may not contribute to overall tumour response, nonapoptotic cell death such as autophagy, which may be triggered by apoptosis, still occurs. Anticancer treatment-induced apoptosis is regulated by the balance of proapoptoic and antiapoptoic proteins through mitochondria, and resistance to apoptosis is mediated by Bcl-2-dependent and Akt-dependent pathways. Bcl-2 partially inhibits nonapoptotic cell death as well as apoptosis, whereas Akt inhibits both apoptotic and nonapoptotic cell death through several target proteins. CONCLUSIONS: Drug sensitivity is likely correlated with the accumulation of apoptotic and nonapoptotic cell deaths, which may influence overall tumour response in anticancer treatment. The ability to predict overall tumour response from the modulation of several important cell death-related proteins may result in a more efficient strategy for improving the therapeutic effect.

Animals↗
PubMed1996

Antithrombin III prevents renal dysfunction and hypertension induced by enhanced intravascular coagulation in pregnant rats: pharmacological confirmation of the benefits of treatment with antithrombin III in preeclampsia.

We tested the hypothesis that enhanced intravascular coagulation in pregnancy could produce clinical symptoms similar to those of preeclampsia, such as hypertension, proteinuria, and edema. Having confirmed this, we then examined whether the pathological changes caused by intravascular coagulation could be suppressed by administration of antithrombin III (AT III), an endogenous inhibitor active to thrombin and factor X a. Intravascular coagulation was induced in Wistar rats on day 16-20 of pregnancy by 1-h arterial infusion of tissue thromboplastin (TP) through the left ventricle of the heart. One hour after the end of the infusion period, organ blood flows were measured by the radioactive ((57)Co-labeled) microsphere method, and fibrin deposition in organs was measured by radiolabeling with [(125)I] fibrinogen injected before TP infusion. Infusion of TP produced fibrin deposition in the kidney, lung, and liver, but not in the myometrium and placenta, as well as an 80% decrease in renal blood flow (RBF), with oliguria and proteinuria. TP also caused an increase in blood pressure (BP) accompanied by an increase in plasma renin activity (PRA), both of which were suppressed by bilateral nephrectomy before TP infusion. The prophylactic administration of AT III concentrates (60 or 300 U/kg intravenously (i.v.), followed by infusion of 30 or 150 U/kg/2 h, respectively) prevented all pathological changes in a dose-dependent manner. AT III increased placental blood flow regardless of the state of coagulation. These findings suggest that intravascular coagulation plays a significant part in the pathophysiology of preeclampsia and that AT III concentrates may have therapeutic potential in the treatment of this condition.

Animals↗
PubMed2006

p75(NGFR) immunostaining for the detection of perineural invasion by cutaneous squamous cell carcinoma.

BACKGROUND: Perineural invasion (PNI) in cutaneous squamous cell carcinoma (CSCC) may portend a poor prognosis for patients. p75NGFR (nerve growth factor receptor) is part of a membrane receptor complex that binds nerve growth factor. Its use for detecting PNI in CSCC in comparison with S-100 immunohistochemical staining has not been explored. OBJECTIVE: To determine whether detection of PNI may be improved by staining with p75NGFR compared with hematoxylin and eosin (H&E) and S-100. METHODS: Thirty-four cases of CSCC were retrospectively evaluated for the presence of PNI using standard H&E, as well as S-100 and p75NGFR immunohistochemical stains. Staining intensity was correlated to the presence or absence of PNI and tumor differentiation. RESULTS: The results showed a positive correlation between staining intensity and the presence of PNI detected by p75NGFR (p=.04). Using p75NGFR allowed for the detection of seven cases of PNI not detected by H&E alone. Five of these cases were detected by S-100, with two cases seen by p75NGFR only. Six cases of PNI were detected using S-100 not seen on H&E, with one case also not seen using p75NGFR. CONCLUSION: p75NGFR immunostaining increased detection of PNI compared with H&E. p75NGFR could serve as an alternative to S-100 in the detection of PNI or as part of an immunostaining panel for PNI detection.

Carcinoma, Squamous Cell↗
PubMed1996

Repressive regulation of the aquaporin-2 gene.

Expression of aquaporin-2 (AQP2) is exclusively limited to kidney collecting duct cells, and this strictly limited expression could be mediated by transcription of the gene. We first examined AQP2 mRNA expression in many cultured epithelial cells derived from kidney. Northern blot using OK, LLC-PK1, Madin-Darby canine kidney, and outer medullary collecting duct (OMCD) cells and primary culture of inner medullary collecting duct (IMCD) cells did not reveal any significant signal. A more sensitive method, ribonuclease protection assay, could detect a faint signal in OMCD cells when they were bathed in a hypertonic medium. Reverse-transcribed polymerase chain reaction applied to primary culture of IMCD cells showed a rapid dissipation of AQP2 mRNA within 4 days after culture. A reporter gene assay performed in the 1st day of primary culture of IMCD cells showed that the 5' region up to -2.9 kb worked as a promoter. Deletion experiments showed that at least two regions, from -434 to -364 and from -153 to -84, contain negatively acting cis-elements. When connected to a heterologous promoter, these regions repressed the activity in an orientation-dependent manner. These results suggest that transcription of AQP2 gene is strictly regulated and its ability is rapidly depressed in culture condition. This cell differentiation-specific expression of the gene may be, at least in part, mediated by the repressors present in its 5'-flanking region.

Animals↗
PubMed1992

Internal jugular vein catheterization in infants undergoing cardiovascular surgery: an analysis of the factors influencing successful catheterization.

Central venous catheterization for pressure monitoring and drug administration is often important in the anesthetic management of infants undergoing cardiovascular surgery. We examined the effects of patient age, weight, and central venous pressure and the experience of the anesthesiologist on the rate of successful catheterization and catheterization time of the internal jugular vein (IJV) in a prospective study. We studied 106 infants undergoing IJV catheterization for cardiovascular surgery over a 7-mo period at our institution. We catheterized the IJV by the high approach. The direct venipuncture or the Seldinger method was used according to the patient's weight. Overall successful catheterization rate was 97.2%, and the average catheterization time was 353 +/- 21 s (mean +/- SEM). Complications included arterial puncture in 12 cases (11.3%), hematoma formation in four cases (3.8%), and catheter malposition in two cases (1.9%), but pneumothorax was not observed. When a patient was younger than 3 mo or weighed less than 4.0 kg, successful catheterization rate decreased significantly to 81.3% and 78.6%, respectively. Catheterization time was inversely correlated with both age and weight, whereas central venous pressure did not affect either successful catheterization rate or catheterization time. We were unable to demonstrate that the experience of the anesthesiologist plays a significant role in the success or complication of the catheterization procedure. Our results indicate that IJV catheterization by the high approach is a reliable and useful technique in infants, and that the weight and age of the patient significantly influence the rate of successful catheterization.

Age Factors↗
PubMed2005

Novel deletion spanning RCC1-like domain of RPGR in Japanese X-linked retinitis pigmentosa family.

PURPOSE: To describe a macrodeletion spanning entire RCC1-like doman in the RPGR gene in one Japanese family with X-linked retinitis pigmentosa (XLRP). METHODS: Clinical ophthalmologic examinations were performed and genomic DNA was extracted from blood samples. Genomic DNA was analyzed by Southern blot and PCR amplification with specific primers. RESULTS: Patients had severe symptoms with early onset and rapid deterioration. PCR amplification and Southern blot analysis revealed the absence of the 5' half of the RPGR gene. The deletion was confirmed and characterized by designing flanking PCR primers: the deletion start point was located 80 bp upstream of the translation start site in exon 1, the end point was 42 bp downstream of exon 11. CONCLUSIONS: This 30 kb deletion contains the exons coding for the RCC1-like domain of RPGR. It is the first report of a macrodeletion that spans the entire RCC1-like domain of RPGR in X-linked retinitis pigmentosa patients, and suggests that loss of function of this domain disrupts the function of RPGR in human retina.

Adult↗
PubMed2000

Usefulness and pitfalls of intraoperative spinal motor evoked potential recording by direct cortical electrical stimulation.

OBJECTIVE: The aim of this study is to investigate the usefulness and problems with spinal motor evoked potential (MEP) recording, especially the reasons for failed recording. We report our personal experience over the last 8 years in patients with lesions adjacent to the primary motor cortex. METHODS: MEP records of 50 consecutive patients were retrospectively reviewed. MEP was recorded by a catheter electrode inserted in the cervical epidural space. Stimulation electrodes were placed on the cortical surface during surgery. SEP recording was also performed in 29 of 50 patients. RESULTS: MEP was obtained in 40 cases, and SEP was recorded in all 29 cases. The central sulcus was identified in 93% of patients in whom both MEP and SEP were performed, whereas in only 86% of patients who underwent only MEP. The main reason for MEP failure were inadequate exposure of the motor cortex, pre-existing hemiparesis and technical errors. Postoperative deterioration of motor function was closely related to intra-operative MEP changes. CONCLUSION: MEP is a useful tool to determine the motor cortex and to predict postoperative motor function. However, precise pre-operative craniotomy planning and combination with intra-operative SEP is essential to reduce the MEP failure.

Adolescent↗
PubMedDate not supplied

Stability of the diagnosis of first-episode psychosis made in an emergency setting.

OBJECTIVE: This study aimed at evaluating the stability of the first psychotic episode diagnosis in the emergency context. METHODS: Fifty-nine patients were selected during a 15-month period and were followed for an average of 19.35 +/- 6.12 months. The admission and discharge emergency diagnosis were compared with the longitudinal diagnosis, obtained by the application of Structured Clinical Interview for DSM-IV Axis I Disorders--clinical version at the end of the follow-up. Severity rating scales (Brief Psychiatric Rating Scale, Young Mania Rating Scale and Hamilton Rating Scale for Depression) were applied in the emergency assessment. RESULTS: Agreement between admission emergency diagnosis and longitudinal diagnosis was unsatisfactory (k=0.25), whereas that between emergency discharge and longitudinal diagnosis was satisfactory (k=0.57). Brief psychotic disorder diagnosis presented higher sensitivity rates but low specificity, comprising several false positives. Bipolar disorder had the highest rates of specificity. CONCLUSION: Brief psychotic disorder may not be a useful concept in the emergency assessment. A short period of observation can improve emergency psychiatric diagnosis.

Adolescent↗
PubMedDate not supplied

Tenascin-C levels in pseudosynovial fluid of loose hip prostheses.

OBJECTIVE: Aseptic loosening is one of the most important problems that can occur after total hip arthroplasty (THA). In this study, we analysed levels of large tenascin-C (TN-C) variants and compared them in pseudosynovial fluid from patients with aseptic loosening after THA with those in synovial fluid from patients undergoing primary THA (control). METHODS: Pseudosynovial fluid samples (n = 24) were obtained by aspiration at the time of revision THA performed due to aseptic loosening. Synovial fluid samples (n = 12) were obtained by aspiration at the time of primary THA. Expression of TN-C splice variants was examined using immunoblotting. TN-C levels were measured using an enzyme-linked immunosorbent assay (ELISA) system that we developed previously. RESULTS: Western blotting showed the presence of large TN-C variants in pseudosynovial fluid of artificial joints with loosening. TN-C levels were approximately three times higher in pseudosynovial fluid of loose artificial joints (median 151.9 ng/mL) than in synovial fluid controls (median 50.1 ng/mL) (p = 0.035). CONCLUSION: Levels of TN-C including large variant subunits are elevated in pseudosynovial fluid of loose artificial joints, indicating that TN-C is a useful novel biochemical marker of loose hip prostheses.

Aged↗
PubMed2006

Effects of driving on low back pain.

BACKGROUND: Many previous studies have demonstrated that driving a car is a risk factor for low back pain (LBP). We have frequent contact with medical representatives who often drive cars for business, and have noticed that many of them suffer from LBP. AIMS: To investigate how driving affected the occurrence of LBP in medical representatives. METHODS: Questionnaire survey of all medical representatives working in Mie Prefecture (Japan). RESULTS: A total of 551 medical representatives replied (92%). We divided the subjects into Group A (with LBP) and Group B (without LBP). There was no significant difference in mean age, height, weight or duration of continuous employment between the two groups. Mean total mileage was 342 539 km in Group A and 251 945 km in Group B (P < 0.05). There was no significant difference in estimated daily mileage or estimated daily driving time between the two groups. As for backrest inclination, most of the respondents in Group A chose 105 degrees and the majority in Group B chose 120 degrees (P < 0.001). CONCLUSION: The total mileage was significantly higher in Group A than in Group B. We considered that the risk for LBP increased as the lumbar spine load accumulated day by day while driving a car almost every day without a holiday.

Adult↗
PubMed2005

Pre-cutting using a noseless papillotome with independent lumens for contrast material and guidewire.

BACKGROUND: The technical success of therapeutic endoscopic retrograde cholangiopancreatography (ERCP) depends on selective cannulation into the bile duct. We have developed a new type of precut papillotome for selective cannulation. METHODS: The newly developed precut papillotome has been equipped not only with a lumen for contrast materials but also with an independent lumen for the guidewire. The operation of the guidewire and the injection of contrast material can be carried out simultaneously. The precut papillotome has a 20-mm-long knife and no leading tip. Half the proximal side of the knife is coated for insulation. RESULTS: Selective biliary cannulation failed in 26 of 293 patients (8.9%) in whom therapeutic ERCP was attempted. We applied the precut papillotome to these 26 patients and selective cannulation was successful in 24 of 26 patients (success rate: 92.3%). No major complications occurred, although mild bleeding, which did not require endoscopic hemostasis or blood transfusion, was observed only in one patient. CONCLUSIONS: Although further studies with a large number of patients are needed to evaluate the efficacy of the papillotome, this papillotome may contribute to increase the safety and the success rate of precutting.

Aged↗
PubMed1998

Three-dimensional power Doppler sonography of tumor vascularity.

The purpose of this study was to assess the value of routine clinical examination using three-dimensional power Doppler sonography of intratumoral blood flow. Twenty-two hepatocellular carcinomas, seven cases of hepatic metastasis, four hepatic hemangiomas, six renal cell carcinomas, two cases of hepatic focal nodular hyperplasia, and one case of splenic metastasis were included in the study. Three-dimensional images were reconstructed by maximum intensity projection method using cine-loop data on a built-in computer in a LOGIQ 500 and a LOGIQ 700 from GE Yokogawa Medical Systems. The three-dimensional images obtained were viewed multidirectionally on a monitor screen. Three-dimensional representations of intratumoral blood flow became available for all tumors approximately 5 s to 30 s after scanning. In every case, the entire vasculature of the tumor was appreciated more easily from three-dimensional images than from cross-sectional two-dimensional images. These three-dimensional images of intratumoral blood flows corresponded to the tumor vessels that could be visualized by angiography at the early arterial phase. Differential diagnosis of hepatic tumors based on distinct difference in their intratumoral vascular structures was performed. Our results suggest that three-dimensional power Doppler sonography can be used for routine clinical examination of tumor vascularity and may provide improved diagnostic information.

Carcinoma, Hepatocellular↗
PubMedDate not supplied

Postoperative adjuvant chemotherapy after radical hepatic resection for hepatocellular carcinoma (HCC).

BACKGROUND/AIMS: This prospective randomized study was aimed to clarify the efficacy of epirubicin after radical hepatic resection for hepatcellular carcinoma (HCC). MATERIALS AND METHODS: One hundred and one patients entered the present study and were randomly allocated to Group A in which UFT (300 mg/day) was given from 5th postoperative week for one year, or Group B in which a bolus injection of epirubicin (40 mg/m2) was given arterially, in addition to the same UFT administration, on day 28. Groups A and B included 40 and 48 eligible cases, respectively. RESULTS: No obvious intergroup differences were observed including prescribed dose of UFT. The 1-, 3- and 5-year survival rates (Groups A vs B) were 82 vs 90%, 50 vs 49% and 35 vs 30% (p = 0.2162). Excluding 4 operative deaths, the recurrence-free survival rates were 65 vs 70%, 32 vs 37% and 14 vs 17% (p = 0.3843). Initial recurrence sites were also similar. CONCLUSIONS: A bolus arterial injection of epirubicin does not change the long term results after radical hepatic resection for HCC.

Aged↗
PubMed1997

Thyroxine-binding globulin and thyroid hormones after resection of hepatocellular carcinoma.

OBJECTIVES: Some human hepatocellular carcinomas (HCCs) produce thyroxine-binding globulin (TBG). High serum TBG levels in such patients may be associated with increased thyroxine (T4) levels. This study aimed to elucidate the serum TBG and thyroid hormone profile in Japanese patients with HCC, to compare the difference between TBG-producing and -nonproducing HCCs, and to investigate the changes in serum TBG level and the thyroid hormone profile after removal of the tumor. METHODS: The 40 subjects included 20 patients with HCC, 10 healthy controls, and 10 operative controls. Serum TBG, 3,5,3'-triiodothyronine (T3), T4, and free T4 were measured serially for 4 wk after resection of HCC in 16 patients and after control operations in 10 patients. Assay methods were a radioimmunoassay for TBG and enzyme immunoassays for T3, T4, and free T4. RESULTS: Values higher than the mean +/- 2 SD of controls were considered abnormally high. Of patients with HCC, 60% had abnormally high TBG values, 65% had abnormally high T3 values, 39% had abnormally high T4 values, and 6% had abnormally high free T4 values. The mean levels of TBG and T3 were significantly higher than those in healthy controls, but no difference was found for T4 and free T4 levels. There were no significant differences in various clinicopathological factors between patients with high TBG levels and those with normal TBG levels. After resection of HCC, serum TBG decreased significantly in patients with high TBG levels but not in those with normal TBG levels. CONCLUSIONS: This study shows that >50% of HCCs in Japanese patients produce TBG; removal of the tumor reduces serum TBG in such cases.

Adult↗
PubMedDate not supplied

Three-dimensional power Doppler sonography of tumor vascularity.

PURPOSE: To assess the clinical value of three-dimensional (3D) power Doppler imaging of intratumoral blood flow. MATERIALS AND METHODS: Two hepatocellular carcinomas (HCC), one renal cell carcinoma, one hepatic focal nodular hyperplasia (FNH), and one iliac bone metastasis of HCC were used. Images were collected by power mode using the GE-Yokogawa LOGIQ 700. Power Doppler images were recorded on S-VHS videotape and fed into a workstation. Flow information was then extracted, and 3D images were constructed by surface rendering. RESULTS: Preparation of 3D images could be accomplished in one minute after feeding flow information into the workstation. Intratumoral vascular structure could be easily evaluated. This 3D imaging was useful for the differential diagnosis of hepatic tumors, especially HCC and FNH, which were confirmed in 3D imaging to have distinctly different intratumoral vascular structures. CONCLUSION: 3D imaging of intratumoral blood flow was possible by 3D processing of the power Doppler images. 3D power Doppler imaging is expected to be helpful for the differential diagnosis of tumors.

Bone Neoplasms↗
PubMed2002

Sentinel lymph node biopsy without axillary dissection after an intraoperative negative histological investigation in 358 invasive breast cancer cases.

BACKGROUND: Sentinel lymph node biopsy (SLNB) is an important treatment option for breast cancer patients, as it can accurately predict axillary status. Our previous study using dye with or without radioisotope showed the accuracy and sensitivity of SLNB to be 97% and 94%, respectively. Based on these results, axillary lymph node dissection (ALND) was eliminated starting in January, 1999 in patients with intraoperatively negative SLNB at our institution. The present study shows the results and outcomes of SLNB as a sole procedure for patients with invasive breast cancer. PATIENTS AND METHODS: Three-hundred-fifty-four patients and 358 cases of invasive breast cancer (4 bilateral breast carcinoma) treated with SLNB alone after an intraoperative negative SLNB were studied prospectively from January 1999 to December 2001. RESULTS: The number of the identified SLNs per case ranged from 1 to 8 (mean, 2.5). Of a total of 358 cases, 297 (83%) were treated with hormone therapy and/or chemotherapy, and 281 (78%) were treated with radiotherapy to the conserved breast (50 Gy+/-10 Gy boost), the axilla (50 Gy), or the both sites. After a median follow-up of 21 (range 6-42) months, no patient developed an axillary relapse. Four cases initially recurred in distant organs and one case in the conserved breast. CONCLUSIONS: Our results indicate that an intraoperative negative SLNB without further ALND may be a safe procedure when strict SLNB is performed. To better assess the safety, however, may require longer follow-up.

Adult↗
PubMed1999

Experimental small bowel transplantation using newborn intestine in rats: II. Revascularization of newborn intestine is independent of vascular endothelial growth factor.

BACKGROUND: Fetal and newborn intestine often are revascularized after subcutaneous transplantation without surgical vascular anastomosis. However, the mechanism of this ability remains unclear. METHODS: First, the ability of natural revascularization in newborn organs was tested. Newborn organs in whole (liver, kidney, heart, intestine, spleen, and pancreas) were grafted i nto the subcuta neous tissue of the adult rat and evaluated histopathologically 2 weeks after transplantation. Second, expression of vascular endothelial growth factor (VEGF) mRNA in the intestinal graft was determined before and after transplantation. Finally, we tested whether the free graft survival of newborn intestine was interrupted by TNP-470, an antiangiogenic agent. RESULTS: Spleen and intestine were revascularized at a higher rate (91.6%, 75%, respectively), and kidney and heart grafts survived at a lower rate (41.7%, 25%, respectively). But all of liver and pancreas grafts failed to be revascularized. VEGF mRNA was not induced in the course of revascularizing. Furthermore, TNP-470 did not interfere with neovascularization of the newborn intestinal graft in vivo. CONCLUSIONS: Each organ had an organ-specific angiogenic activity. Neovascularization of intestinal graft was not dependent on VEGF expression.

Angiogenesis Inhibitors↗
PubMed2003

Complement fragment C4d deposition in peritubular capillaries in acute humoral rejection after ABO blood group-incompatible human kidney transplantation.

BACKGROUND: Acute humoral rejection (AHR) is the most important risk factor for early graft loss in ABO-incompatible (ABO-i) kidney transplantation (RTx). The pathogenesis and diagnostic criteria for AHR after ABO-i RTx remain unclear. Complement fragment C4d deposition in peritubular capillaries (PTC), which is a sensitive indicator for activation of the classical complement pathway, was studied to establish the pathologic diagnostic indicator of AHR. METHODS: Forty-four graft biopsy specimens from 19 patients with ABO-i living donors were analyzed within 90 days after RTx. Nineteen biopsy specimens with acute rejection after ABO-compatible (ABO-c) living-related RTx were used as controls. Diffuse and bright C4d deposition in PTC was considered significantly positive. RESULTS: All of 8 recipients with AHR showed significantly positive C4d in PTC in the ABO-i group, but 9 of 11 recipients without AHR were negative. In the ABO-c RTx group, 16 of 19 recipients were negative for C4d in PTC. The prevalence of C4d in PTC was significantly higher in ABO-i RTx (P<0.05). CONCLUSIONS: C4d deposition is valuable as a specific and sensitive indicator for AHR, even of mild severity, in ABO-i RTx.

ABO Blood-Group System↗