Expression of β-catenin in normal breast tissue and breast carcinoma: a comparative study with epithelial cadherin and α-catenin

Expression of β-catenin was investigated in normal breast tissue and 66 breast carcinomas in conjunction with expression of epithelial cadherin (E-CD) and α-catenin. In normal mammary ducts and acini, intense β-catenin immunoreactivity was present at the basolateral surfaces of luminal epithelium and weak immunoreactivity was observed at the lateral borders of myoepithelial cells. No β-catenin was revealed at the myoepithelial basal surface. The intercellular expression of β-catenin, as well as of E-CD and α-catenin, was also observed in carcinoma tissues with varying staining intensity. Almost all of 10 intraductal carcinomas and approximately 70% of 41 invasive ductal carcinomas expressed the three molecules at the same level as in normal glands, whereas approximately 80% of 13 invasive lobular carcinomas showed severe deficiency of them. Two lobular carcinomas in situ showed complete absence of all of the proteins. Some of these findings were confirmed biochemically by immunoblotting analysis. In invasive ductal carcinomas, α-catenin was reduced more frequently in diffuse than in solid type tumours, whereas the level of expression of β-catenin and E-CD was unchanged between them. No correlation was present between reduced expression of the adhesion molecules and lymph node metastasis.     

Differences in clinical characteristics between Tourette syndrome patients with and without 'generalized tics' or coprolalia

Abstract  The purpose of this study is to examine whether there are differences in clinical characteristics between Tourette syndrome (TS) patients with and without 'generalized tics' (GT) which involve the entire body, and/or coprolalia. Subjects were 64 patients (55 males and 9 females, mean age, 17.4 ± 7.2 years) who visited Tokyo University's outpatient clinic of neuropsychiatry from 1974 to 1993 and who met criteria for Tourette's disorder of DSM-III-R. Data on clinical characteristics, including tic symptoms and courses of their development, complications and developmental histories, treatment and severity, were collected by systematic chart review of all subjects. Tourette syndrome patients with 'generalized tics' tended to show multiple complex vocal tics more frequently than TS patients without GT. Tourette syndrome patients with coprolalia tended to show significantly higher rates of copropraxia, echolalia, and 'cleaning/washing' compulsion than did the TS patients without coprolalia. Tourette syndrome patients with both GT and coprolalia were classified as the severest group in terms of tic symptoms and social impairment. Tourette syndrome patients who had neither of these morbidities were classified into the mildest group in all aspects. Generalized tics and coprolalia seemed to indicate the severest end of the TS spectrum and seemed to be related with a need of intensive treatment.     

Basic study on velocity-flow urodynamics using Doppler sonography: Simultaneous detection of cavitation and Doppler signals in an artificial urethral model

BACKGROUND: We have developed velocity-flow urodynamics using Doppler sonography based on the hypothesis that microbubbles formed in the urethra are responsible for Doppler signals. In order to confirm this hypothesis derived from Bernoulli's principle, we investigated the simultaneous detection of cavitation noise and Doppler signals in an experimental system. METHODS: An experimental circuit was built in which a stenosis was created using a glass or silicon tube with tap water used as the sample fluid. Doppler signals, pressure before and after the stenosis, flow rate, flow velocity and cavitation noise were measured. Direct detection of cavitation with a high-speed charged-coupled device (CCD) camera was conducted in the glass tube. The relationship between cross-sectional area and flow velocity in terms of the detection of Doppler signals was analyzed in the silicon tube study. RESULTS: In the glass tube study, a high-speed CCD camera clearly detected masses of microbubbles associated with cavitation. The range of flow rates creating cavitation completely corresponded with those producing Doppler signals detected by ultrasonography. A similar correlation was observed in the silicon tube study, which showed that a low flow velocity of 41.5 cm/sec through a stenosis with a cross-sectional area of 20 mm(2) created Doppler signals at a flow rate of 8.3 mL/sec. CONCLUSION: The results of the present study confirmed that microbubbles created in flowing urine are responsible for Doppler signals. Measurement of velocity-flow urodynamics has great potential to become a non-invasive and reliable alternative to conventional pressure- flow urodynamic studies.     

Prevalence of hepatitis C virus antibody in an area endemic for hepatitis B virus and human T cell leukaemia virus

To clarify the prevalence of concurrent infection with hepatitis C virus (HCV), hepatitis B virus (HBV) and human T cell leukaemia virus (HTLV), we measured HCV antibody in the population of a district endemic for HBV and HTLV infection. Blood samples were collected in June 1990 from 579 inhabitants of four islands of Uwa Bay in the southwest of Ehime Prefecture in Japan. Anti-HCV antibody against C100-3 protein was detected using an enzyme-linked immunosorbent assay kit (Ortho Diagnostics). Thirteen of the 579 inhabitants (2.2%) were positive for anti-HCV, and this prevalence rate was not significantly different from the frequency of anti-HCV in Tokyo blood donors. A total of 11% (64 of 579) of the subjects were positive for HBsAg and 3.3% (19 of 579) were positive for anti-HTLV. These frequencies of HBsAg and anti-HTLV positivity were distinctly higher than the respective means of Japanese. All anti-HCV positive individuals were negative for HBsAg and anti-HTLV, while 54% (7 of 13) had increased alanine aminotransferase levels. These data suggest that the prevalence of HCV infection is not high even in an area endemic for HBV and HTLV infection.     

Laparoscopic radical cystectomy and bilateral ureteric ligation for muscle-invasive bladder cancer in a patient on hemodialysis

Laparoscopic cystectomy and bilateral ureteric ligation were performed on a 52-year-old woman with end-stage renal disease on hemodialysis (HD) for muscle-invasive bladder cancer. Her volume of urine production was approximately 100 mL/day. Excisions of the bladder and uterus with ligation of the bilateral ureter were conducted completely laparoscopically. Total operative time was 280 min and the amount of blood loss was 60 mL. No complications were seen perioperatively and no adverse events regarding ureteric ligation arose. HD was performed on the second postoperative day. At a 12-month follow-up, the patient showed no evidence of disease.     

Chemokine receptor CCR6 as a prognostic factor after hepatic resection for hepatocellular carcinoma

Background and Aims: Chemokines and their receptors have recently been shown to have major roles in cancer metastasis. The aim of this study was to determine whether the interaction between chemokine receptor 6 (CCR6) and its ligand, macrophage inflammatory protein‐3 alpha (MIP‐3α), correlates with metastasis of hepatocellular carcinoma (HCC). Methods: To observe the reaction of CCR6 expressed cancer cells to MIP‐3α stimulation, chemotactic and actin polymerization assays for both CCR6 high cells (HepG2) and CCR6 low cells (MCF‐7) were performed. CCR6 mRNA levels in tumor specimens from 30 HCC patients were quantified by real‐time polymerase chain reaction. Patients were classified into two groups, high (≥ 20 copies; n = 10) CCR6 and low (<20 copies; n = 20) CCR6 on the basis of CCR6 expression, and the groups were compared with respect to clinicopathological features. Results: When HepG2 cells (CCR6 high) were stimulated with MIP‐3α, they migrated in a dose‐dependent manner, and formation of pseudopodia was observed. These phenomena were not observed in the CCR6 low cells. The incidence of intrahepatic metastasis was higher in the high CCR6 expression group than in the low CCR6 expression group (P < 0.05). Disease‐free survival was significantly poorer in the high CCR6 expression group than in the low CCR6 expression group (P < 0.05). Conclusions: It was indicated that CCR6 might be associated with intrahepatic metastasis of HCC and might be able to become one of the prognostic factor after hepatic resection for HCC.     

YF476 is a new potent and selective gastrin/cholecystokinin-B receptor antagonist in vitro and in vivo

Background : We newly synthesized YF476 ((R)-1-[2,3-dihydro-2-oxo-1-pivaloylmethyl-5-(2'-pyridyl)-1H-1,4-benzodiazepin-3-yl]-3-(3-methylamino-phenyl)urea) as a gastrin/cholecystokinin-B (CCK-B) receptor antagonist. We investigated the pharmacological profile of YF476 in vitro and in vivo .
Methods : We examined the binding properties of YF476 to the rat brain, cloned canine and cloned human gastrin/CCK-B receptors, and the effect of YF476 on secretagogue-induced gastric acid secretion in rats and Heidenhain pouch dogs.
Results : YF476 replaced the specific binding of [¹²⁵I]CCK-8 to the rat brain, cloned canine and cloned human gastrin/CCK-B receptors, with K _i values of 0.068, 0.62 and 0.19 n M , respectively. The affinity of YF476 for rat brain gastrin/CCK-B receptor was 4100-fold higher than that for rat pancreatic CCK-A receptor. In anaesthetized rats, intravenous YF476 inhibited pentagastrin-induced acid secretion with an ED ₅₀ value of 0.0086 μmol/kg, but did not affect histamine- and bethanechol-induced acid secretion at a dose of 10 μmol/kg. In Heidenhain pouch dogs, intravenous and oral YF476 inhibited pentagastrin-stimulated gastric acid secretion in a dose-dependent manner with ED ₅₀ values of 0.018 and 0.020 μmol/kg, respectively, but did not affect histamine-induced acid secretion.
Conclusion : These results suggest that YF476 is an extremely potent and highly selective gastrin/CCK-B receptor antagonist, and that the gastrin/CCK-B receptor is not involved in histamine- or bethanechol-induced gastric acid secretion in dogs or rats.     

Expression of oncogene products, anti-oncogene products and oncofetal antigens in intraductal papillary-mucinous neoplasm of the pancreas

A few previous studies have demonstrated the expression or mutations of oncogenes and anti-oncogenes as well as that of oncofetal antigens in intraductal papillary-mucinous neoplasm of the pancreas. In this study, we have investigated the immunohistochemical expression of oncogene (ras and c-erbB-2) and anti-oncogene (p53 and retinoblastoma [Rb]) products and oncofetal antigens (CEA, CA19-9 and DUPAN-2) in nine such tumours of the pancreas. In normal pancreas (5 cases), the Rb gene product and CA19-9 were expressed in all cases, while ras and c-erbB-2 gene products, p53 protein, CEA and DUPAN-2 were not expressed. In intraductal papillary-mucinous tumours (n = 9), ras, c-erbB-2, p53 and Rb gene products were present in 4/9 (44%), 7/9 (78%), 0.9 (0%) and 6/9 (67%) cases, respectively. CEA, CA19-9 and DUPAN-2 were expressed in 8/9 (89%), 9/9 (100%) and 2/9 (22%) cases respectively. In invasive ductal adenocarcinoma of the pancrease (7 cases), ras, c-erbB-2, p53 and Rb gene products were expressed in 3/7 (43%), 6/7 (86%), 2/7 (29%) and 3/ & (43%) cases respectively. CEA, CA19-9 and DUPAN-2 were expressed in 7/7 (100%), 7/7 (100%) and 6/7 (86%) cases, respectively. The extent and intensity of the expression of these antigens was greater in invasive ductal adenocarcinomas. These data suggest that activation of ras and c-erbB-2 oncogenes and inactivation of Rb anti-oncogene may contribute to the development and progression of intraductal papillary-mucinous tumours of the pancreas and that there is neo-expression of CEA and DUPAN-2 during the development and progression of these tumours.     

Effect of hypothermia on the in vitro potencies of neuromuscular blocking agents and on their antagonism by neostigmine

The effect of temperature on the potencies of neuromuscularblocking agents remains unclear. This study was undertaken toexamine the effects of different neuromuscular blocking agentsat 37 and 27 °C at a constant carbon dioxide content ( statprinciple). The effect of neostigmine 1 µmol litre^–1induced antagonism of these agents was also investigated. Phrenicnerve-hemidiaphragm preparations of rats were mounted in modifiedKrebs solution, maintained at 37 CC and aerated with a 5% carbondioxide-95% oxygen gas mixture, and at 27 °C with 4% carbondioxide to maintain the carbon dioxide content of the solutionconstant. Phrenic nerves were stimulated with 0.1 -Hz supra-maximalimpulses of 0.2-ms duration and the elicited tension of thediaphragm recorded. The potencies of the steroidal neuromuscularblocking agents (rocuronium, vecuronium, pancuronium and pipecuronium)increased significantly at 27 °C (P<0.05), while thepotencies of the benzyliso-quinolinium agents (tubocurarineand dimethyl-tubocurarine) did not change. Neostigmine-inducedantagonism of the steroidal agents did not differ significantlybetween each other but differed significantly from the benzylisoquinoliniumagents (P<0.05) at both temperatures. The ratios of IC₅₀(inhibitory concentration, 50%) with and without neostigmineat hypothermia were slightly higher for the steroidal agents,indicating slight enhancement of antagonism by neostigmine at27 °C. In contrast, the ratios were significantly greaterat 27 °C (P<0.05) for isoquinolinium agents, implyingsignificant enhancement of antagonism. Our results indicatethat at 27 °C the potency of all steroidal agents increasedand neostigmine-induced antagonism was slightly enhanced. Withthe isoquinolinium agents, hypothermia caused no change in potencyalthough neostigmine-induced antagonism was enhanced significantly.These findings suggest that the relative effects of steroidaland isoquinolinium agents on the neuromuscular junction aredifferent or that they have a different mechanism of actionon the neuromuscular junction.