Expression of Immunoreactive E-Cadherin Adhesion Molecules in Human Cancers

E-cadherin (E-CD), a Ca(2+)-dependent adhesion molecule, plays a major role in the maintenance of intercellular junctions in normal epithelial cells in most organs. The expression of E-CD in human carcinoma samples (esophagus, stomach, and breast) was investigated using immunohistochemical staining, which was performed on surgical specimens using a monoclonal antibody for human E-CD. E-cadherin was strongly expressed in all normal epithelium examined. However E-CD expression in primary tumors of esophagus (11 of 15: 73%), stomach (5 of 20: 25%), and breast (9 of 20: 45%) was reduced, and 68% of these (esophagus: 8 of 11, stomach: 4 of 5, breast: 5 of 9) displayed heterogeneous E-CD expression. In some tumor cells with reduced E-CD expression, E-CD molecules were located in the cell cytoplasm. These results indicate that there are human cancer cells in which E-CD-related intercellular adhesion is impaired.     

First trimester prenatal diagnosis of haemophilia a using factor VIII gene probe

Accurate first-trimester prenatal diagnosis was achieved in a Japanese haemophilia A family by the use of a restriction fragment length polymorphism (RFLP) located within the F.VIII gene. Since the pregnant woman's heterozygosity forBclI polymorphism in F.VIII/intron 18 (F8A) probe was informative, chorionic villus sampling (CVS) was performed at 9 weeks of gestation. Restriction analysis showed that the fetus was heterozygous for theBclI site and had received a normal paternal X chromosome (0.9 kb) and a normal maternal X (1.2 kb). Therefore, we concluded that the fetus was a non-carrier female. Pregnancy went to term and woman gave birth to an apparently healthy female. At one week after birth a coagulation study confirmed that the newborn infant is not a carrier. The first-trimester prenatal diagnosis of haemophilia A is possible by CVS due to a RFLP in the F.VIII gene.     

Comparison of histological changes and changes in nm23 and c-MET expression between primary and metastatic sites in osteosarcoma: a clinicopathologic and immunohistochemical study

Changes in morphological features between the primary and metastatic sites in osteosarcoma and the role of nm23 protein and c-MET oncogene product have remained controversial. In addition to histological studies, we evaluated the expression of nm23, c-MET, p53, and MDM2 immunohistochemically using 25 osteosarcomas in which both primary and concordant metastatic specimens were available. Moreover, we assessed proliferative activity using the monoclonal antibody MIB-1. Among these 25 cases, 4 tumors that were osteoblastic type (16%) in the primary site had changed morphologically to MFH-like type in the metastatic site, whereas 2 MFH-like type and 1 small cell-type tumors had changed to osteoblastic type. MIB-1 LI was significantly higher in the metastatic site than in the primary site (primary, 20.02; metastatic, 26.72; P = .0209). Seventeen cases (68%) showed increased nm23 expression in the metastatic site, whereas 2 cases showed reduced expression. nm23 expression was significantly increased in the metastatic site, compared with the primary site (P = .0009). Seven cases (28%) showing negative reaction for c-MET in the primary site showed immunuoreactivity for c-MET in the metastatic site. Although there was no statistical significance, c-MET expression seemed to be more frequent in the metastatic site, compared with the primary site. Among the overall tumors, c-MET-positive tumors showed significantly higher MIB-1 LI, compared with c-MET-negative tumors (negative, 20.99; positive, 27.65; P = .0292). No significant change was observed regarding p53 and MDM2 between the primary and metastatic site. Our results suggest that rather than being a metastasis-suppressor gene, nm23 is in fact correlated with metastatic progression in osteosarcoma. Positive correlation between c-MET expression and proliferative activity also suggests that c-MET expression may play an important role in tumor progression in osteosarcomas.     

The mechanism of the initiation reaction of the cationic polymerization of tetrahydrofuran by stable cationic salts

The mechanism of the initiation reaction for the polymerization of cyclic ethers and lactones by triethyloxonium-, acetyl- and dioxolenium-salts was studied. Triethyloxonium salts initiate the polymerization of cyclic ethers simply by the alkyl exchange reaction. Cyclic esters react with triethyloxonium salts at both ether and carbonyl oxygens but the polymerization proceeds by the acyl-oxygen fission. The k_p value of the polymerization of THF by triethyloxonium salts is almost constant independent of gegenanion. Acetyl cation initiates the polymerization of THF partly by bonding mechanism, but dioxolenium salt initiates completely by bonding.     

Generation and transformation of second-order nonlinearity in catfish retina

A large part of the response from catfish retinal neurons evoked by a white-noise modulated light stimulus is reconstructed by the linear and the second-order nonlinear components, which shows that the first- and second-order kernels represent the major response characteristics. In catfish retina, amacrine cells are classified as type-C and type-N cells. Type-C cells produce a stable and stereotyped second-order kernel that can be reproduced by squaring an underdamped first-order kernel. This is a linear filter followed by a static nonlinearity and is modeled by a cascade of the Wiener structure. A second-order kernel from the other class of amacrine cells, type-N cells, is reproduced by a simple linear filtering of type-C cell response. This is a static non-linearity sandwiched between two linear filters and is modelled by a cascade of the Korenberg structure. These findings may greatly simplify future attempts to reconstruct retinal circuitry and may give some insight into the process of complex signal processing in the inner part of the vertebrate retina.     

New ligands for human C-reactive protein: calcium-dependent binding with epsilon-aminocaproic acid-agarose and calcium-independent binding with omega-aminohexyl-agarose

Human C-reactive protein (CRP) is an acute phase protein which increases in concentration in response to inflammation. CRP has been known to bind with phosphorylcholine in a calcium-dependent manner. In this study, CRP is found to bind to affinity chromatography of negatively-charged epsilon-aminocaproic acid-agarose when calcium ions are present, and to the affinity chromatography of positively-charged omega-aminohexyl-agarose if a normal ionic strength of NaCl exists but calcium ion is not present.     

Current circulatory support with step-by evaluation of biventricular and pulmonary function

The purpose of this study was to examine the clinical results of current circulatory support with step-by evaluation of biventricular and pulmonary function. Six patients who had undergone cardiac surgery and two non-cardiotomy patients underwent current circulatory support with the step-by functional evaluation. Of six postcardiotomy patients, four patients with severe ischemic heart disease underwent coronary artery bypass giafting (CABG), and the remaining two patients with advanced aortic stenosis underwent aortic valve replacement (AVR). All six patients received intra-aortic balloon pump (IABP) support before or during operation. Two non-cardiotomy patients suffered from dilated cardiomyopathy, and both showed acute deterioration with cardiogenic shock or low cardiac output syndrome. Three of six postcardiotomy patients with circulatory support were weaned and discharged from the hospital. Two noncardiotomy patients in critical condition were successfully supported for more than 6 months by the Novacor left ventricular assist system (LVAS). We conclude that the ongoing current strategy of circulatory support with step-by functional evaluation might be applied for various types of severe heart failure with or without associated cardiac operations.     

Management of nodular goiters and their operative indications

It remains controversial whether or not nodular goiters should be treated surgically or conservatively. This report reviews our 9-year experience of treating nodular goiters in 334 patients, 44 of whom underwent surgery, and compares the methods of treatment employed from 1990 to 1999 with those employed from 1971 to 1989 when 171 operations were carried out. In accordance with diagnoses made using fine-needle aspiration biopsy (FNAB) and ultrasonography, patients were treated as follows. Those with cysts were given percutaneous ethanol injection therapy (PEIT), and those with solid tumors underwent surgery if cancer of >class 3 was suspected or if the tumors were >3 cm. Consequently, 44 patients with solid tumors underwent surgery and 72 with cysts were treated by PEIT. The number of operations performed annually decreased to half of the pre-1990 figure. During the follow-up of those patients who did not undergo surgery, four with solid tumors and two with cysts later required surgery due to suspected carcinoma of >class 3 in 3 patients or as a result of personal choice in 3 patients. The growth of solid tumors was not able to be measured in most cases. These results indicate that the number of operations performed for nodular goiters can be reduced by PEIT. An accurate cytological diagnosis supports this therapeutic strategy. Received: August 18, 1999 / Accepted: March 24, 2000     

Small-field radiotherapy in combination with concomitant chemotherapy for locally advanced pancreatic carcinoma.

PURPOSE: To evaluate the effectiveness of small-field radiotherapy in combination with concomitant 5-fluorouracil (5FU) or cisplatin for locally advanced pancreatic carcinoma. MATERIALS AND METHODS: From November 1993 to January 1999, 53 patients underwent continuous 5FU infusion at 200mg/m2 (27 patients) or a 30-min cisplatin infusion at 5mg/m2/day (26 patients) just prior to each irradiation. The radiation field was limited to cover the primary and the paraaortic regions at celiac and supramesenteric axis levels. A total dose of 50.4Gy in 28 sessions was given in 5.6 weeks. RESULTS: Median and 1-year survival rates were 10.2 months and 35.2%, respectively. Local failure occurred in 19 patients (36%) and liver metastases in 16 patients (30%). All local recurrences occurred only within the radiation field. CONCLUSIONS: Median survival rates were comparable to other studies. Because local failure occurred only within the radiation field, the use of relatively small-field radiotherapy may be justified in the treatment of locally advanced pancreatic carcinoma in addition to concurrent administration of either 5FU or cisplatin.     

Reduced expression of p53 and cyclin A in intraductal mucin-hypersecreting neoplasm of the pancreas compared with usual pancreatic ductal adenocarcinoma

OBJECTIVE: Intraductal mucin-hypersecreting neoplasm (IMHN) of the pancreas, a slow-growing malignancy with a favorable prognosis, is distinctly categorized from the high-grade malignancy of the more common ductal adenocarcinoma. The aim of the present study was to clarify the molecular differences underlying the biological differences between IMHN and ductal adenocarcinoma of the pancreas. METHODS: The expression of p53 and cyclin A in IMHN was compared with that in ductal adenocarcinoma of the pancreas immunohistochemically. RESULTS: In IMHN, the incidence of p53 and cyclin A ascertained by positive nuclear staining was significantly lower than that in ductal adenocarcinoma. Furthermore, in ductal adenocarcinoma, p53 and cyclin A are topographically coexpressed. CONCLUSIONS: These results suggest that the overexpression of p53 and cyclin A plays a role in the tumorigenesis of pancreatic ductal adenocarcinoma, and sparse expression of both antigens in IMHN may partly contribute to its low-grade malignant characteristics.