Copolymerisation of ethylene with polar monomers by using palladium catalysts bearing an N-heterocyclic carbene-phosphine oxide bidentate ligand.

We report the synthesis and characterisation of palladium complexes bearing an N-heterocyclic carbene-phosphine oxide bidentate ligand and their use as catalysts for ethylene polymerisation and ethylene/polar monomer copolymerisation.

Polypeptide N-acetylgalactosaminyl transferase 3 independently predicts high-grade tumours and poor prognosis in patients with renal cell carcinomas.

BACKGROUND: The polypeptide N-acetylgalactosaminyltransferases (GalNAc-Ts) family of enzymes regulates the initial steps of mucin-type O-glycosylation. N-acetylgalactosaminyltransferases might show novel patterns of GalNAc-T glycosylation on tumour-derived proteins, which could influence cancer biology, but its mechanisms are unclear. We investigated the association of GalNAc-T3 and -T6 expressions with clinicopathological features and prognoses of patients with renal cell carcinomas (RCCs). METHODS: Expressions of GalNAc-T3/6 and cell-adhesion molecules were analysed immunohistochemically in 254 paraffin-embedded tumour samples of patients with RCC. RESULTS: Of 138 GalNAc-T3+ cases, 46 revealed significant co-expression with GalNAc-T6. N-acetylgalactosaminyltransferases-3+ expression showed a close relationship to poor clinical performance and large tumour size, or pathologically high Fuhrman's grading, and presence of vascular invasion and necrosis. The GalNAc-T3-positivity potentially suppressed adhesive effects with a significantly low ß-catenin expression. Univariate and multivariate analyses showed the GalNAc-T3+ group, but not the GalNAc-T6+ group, to have significantly worse survival rates. CONCLUSION: N-acetylgalactosaminyltransferases-3 expression independently predicts high-grade tumour and poor prognosis in patients with RCC, and may offer a therapeutic target against RCC.

Polypeptide N-acetylgalactosaminyltransferase 6 expression in pancreatic cancer is an independent prognostic factor indicating better overall survival.

BACKGROUND: The family of polypeptide N-acetylgalactosaminyltransferases (GalNAc-Ts) is responsible for the altered glycosylation in cancer. The purpose of our study was to investigate the clinical significance of two isoforms, GalNAc-T6 and -T3, and their correlation with the prognosis of pancreatic cancer. METHODS: Immunohistochemistry was used to analyse GalNAc-T6 and -T3 expressions in 70 clinicopathologically characterised pancreatic cancer cases. RESULTS: Positive expressions of GalNAc-T6 and -T3 were immunohistochemically identified in 51% (36 of 70) and in 77% (54 of 70) of patients, respectively. A close relationship was noted between GalNAc-T6 positive expression and pathological well/moderate differentiated type (P=0.001), small tumour size (P=0.044), absence of vascular invasion (P=0.009), and low stage of the American Joint Committee on Cancer systems (P=0.043). The expression of GalNAc-T3 significantly correlated with good differentiation (P=0.001), but not with other clinicopathologic features. Furthermore, univariate and multivariate analyses revealed that GalNAc-T6 expression was an independent prognosis indicator for the disease, whereas GalNAc-T3 expression had no impact on clinical outcome, even though 33 of 36 GalNAc-T6-positive cases also had a positive expression of GalNAc-T3 (P=0.001, r=0.356). CONCLUSION: Both GalNAc-T6 and -T3 expressions correlated significantly with tumour differentiation, whereas only GalNAc-T6 expression predicted prognosis in pancreatic cancer.

Psoriasiform skin lesion and supprative acrodermatitis associated with Kawasaki disease followed by the treatment with infliximab: a case report.

UNLABELLED: A 4-month-old boy was diagnosed with Kawasaki disease. The ordinary treatments with intravenous gammaglobulin and metylpredonisolone were not effective. Infliximab (5 mg/kg) was administrated on 13th day of illness which led to defeverscence and improvement of clinical manifestations. On 23 days of illness, however, desquamative papules and plaques developed on both the extensor surfaces of the forearms and legs. In addition, typical subungual desquamations of fingers and toes followed crusted hyperkeratosis which resembled supprative acrodermatitis. Skin biopsy from the forearm showed inflammatory dyskeratosis with marked hyperkeratosis, epithelial parakeratotsis, loss of granular layer and dominant infiltration of CD8 + T-cells. Local treatment of steroid followed improvement of skin lesions within a few weeks. CONCLUSION: Although previous reports described the beneficial effects of infliximab in patients with Kawasaki disease, it is possible that the administration of infliximab modify psoriasiform skin lesion associated with Kawasaki disease.

Adult colonic intussusception: a case report.

Intussusception accounts for almost all cases of intestinal obstruction in children. In contrast, intussusception in adults is relatively rare. An 86-year-old Japanese female with rectal bleeding came to our hospital via ambulance. At first, colonoscopy findings revealed the sigmoid colon cancer. Ultrasonography showed a hypoechoic mass with a multiple concentric ring sign. Computed tomography showed a round fluid-filled cystic structure. Colon contrast studies demonstrated stenosis in the rectosigmoid colon. A laparotomy was performed. The sigmoid colon was intussuscepted to the rectosigmoid colon. We employed both rectosigmoid and sigmoid colon resection. The resected specimen showed that the disease was advanced sigmoid colon cancer with ulcer formation due to an ischemic change. Tumor was 4.5 cm x 2.0 cm in size. The disease was histopathologically diagnosed as advanced sigmoid colon cancer, well-differentiated adenocarcinoma. We report here a case of adult intussusception due to the sigmoid colon cancer.

Decreased type III and V collagen expression in chorionic villi of hydatidiform mole.

To investigate the characteristic structure of hydatidiform mole, various types of collagen expression were determined in human villous tissues obtained from normal pregnancies (n = 17) and complete hydatidiform moles (n = 10). Indirect immunofluorescent staining was performed to detect type I, III, and VI collagen with specific monoclonal antibodies. Collagens were also extracted from the villous tissues obtained from normal pregnancy and hydatidiform mole by the salt precipitation method. Immunohistochemical staining for type I, III, and VI collagen revealed weak staining of the villous stroma in hydatidiform mole compared with that in normal pregnancy. Both the ratios of type III to type I collagen and the ratios of type V to type I collagen in the villous tissues were significantly decreased (P < 0.05) in molar pregnancy compared with those in normal pregnancy. These results suggest that alterations in the distribution and composition of collagen might play an important role in determining the pathophysiology and structure of hydatidiform mole.

Overexpression of type IV collagen in chorionic villi in hydatidiform mole.

To investigate the characteristic structure of hydatidiform mole, type IV collagen expression was determined in human villous tissues obtained from normal pregnancies (n = 17) and complete hydatidiform moles (n = 10). Indirect immunofluorescent staining was performed to detect type IV collagen with specific monoclonal antibody, and Northern blot analysis was performed to assess expression of messenger ribonucleic acid for the alpha1(IV) chain. In addition, serum levels of type I, III, and IV collagen were measured by RIA. Immunohistochemical staining for type IV collagen revealed stronger staining of the trophoblastic basement membrane in hydatidiform mole than in normal pregnancy. Northern blot analysis revealed that the villous expression of messenger ribonucleic acid for the alpha1(IV) chain was significantly increased in hydatidiform moles compared with normal pregnancy (P < 0.01). Although there were no differences in the serum type I and III collagen levels between hydatidiform mole and normal pregnancy, the type IV collagen level was significantly higher in patients with hydatidiform mole than in normal pregnancy (P < 0.05). These results suggest that type IV collagen might play an important role in determining the pathophysiology and structure of hydatidiform mole.

A struma ovarii with increased serum basement membrane components: a case report.

We report a case of struma ovarii with hyperthyroidism and elevated serum concentrations of type IV collagen and laminin. Circulating levels of type IV collagen and laminin were measured using specific radioimmunoassays (RIAs) for 7S collagen and the P-1 fragment of laminin, and the basement membrane components in the tumor were investigated by immunohistochemical analysis. Strong immunohistochemical staining specific for type IV collagen and for laminin was observed to be localized in the follicular walls. The serum levels of these antigens, as determined by RIA, were very high before removal of the tumor but decreased rapidly postoperatively. The present findings suggest that struma ovarii produces large amounts of type IV collagen and laminin. In addition, elevated levels of thyroid hormones might enhance the turnover of the basement membrane in various tissues.

[Monitoring of the cryptococcus count in the cerebrospinal fluid with negative cultures in two cases of serious cryptococcal meningitis].

We monitored the cryptococcus count in the cerebrospinal fluid(CSF) using the filter technique in two cases of serious cryptococcal meningitis during the course of treatment with antifungal agents. Lumbar puncture was performed once a week, and 1 ml of CSF was filtered through a Millipore filter(5.0-micron pore for cells), followed by staining of the filters with Alcian blue. All of the cryptococci on the filter were counted under a light microscope at a magnification of x 100. More than 500/ml and 2,000/ml of cryptococci were still observed in the CFS in Cases 1 and 2, respectively, in whom CFS cultures for Cryptococcus neoformans became negative after 4 weeks of treatment. Even though the treatment with antifungal agents were continued in these cases, cryptococci could still be observed for 5 weeks and 60 weeks on the filter preparations of Cases 1 and 2, respectively, after the CSF cultures became negative. The cryptococcal antigen could also be detected in the CSF during the positive filter preparations in these cases. At autopsy in Case 2, patchy lepromeningeal inflammatory lesions with the characteristic capsules of cryptococci were observed in the subarachnoid space. These observations suggest that cryptococci, which persisted in the CSF despite the negative cultures, were responsible for the lesions in the subarachnoid space and protracted clinical course in the two cases of cryptococcal meningitis.

The vascular endothelial growth factor/fms-like tyrosine kinase system in human ovary during the menstrual cycle and early pregnancy.

In human ovaries, angiogenesis is known to be associated with the development of follicles and the formation of the corpus luteum (CL). A complex vascular network is formed within the thecal cell layer during follicular growth, and rapid neovascularization occurs toward the granulosa cell layer after ovulation. Vascular endothelial growth factor (VEGF) is a multifunctional cytokine, stimulating endothelial cell growth and enhancing microvascular permeability. A specific receptor for VEGF, fms-like tyrosine kinase (Flt-1), is expressed in vascular endothelial cells that mediates the action of VEGF. We examined the localization and expression of VEGF and Flt-1, using an immunohistochemical technique and RT-PCR analysis, in human follicles and corpora lutea during the normal menstrual cycle and early pregnancy. We measured concentrations of VEGF in extracts of human CL using an enzyme-linked immunosorbent assay during the luteal phase and early pregnancy. Immunostaining for VEGF was observed in granulosa cells from small antral follicles to preovulatory follicles. The staining was detected in thecal cells from medium-sized to preovulatory follicles. The intensity of the staining was gradually increased as a follicle grew. Flt-1 was localized in granulosa and thecal cells of preovulatory follicles as well as in endothelial cells. In the human CL, the intense staining for VEGF was observed in granulosa and thecal lutein cells, especially in the midluteal phase. The immunostaining for Flt-1 was faint in endothelial cells in the CL, whereas it was distinct in granulosa and thecal lutein cells. The concentrations of VEGF in lutein extracts were high in the early and midluteal phases and tended to decrease toward the late luteal phase. During early pregnancy, a measurable amount of VEGF was detected. RT-PCR analysis demonstrated that messenger ribonucleic acids encoding VEGF121, VEGF165, and Flt-1 were expressed in the CL. These results suggest that VEGF might have an autocrine role in the ovulatory process and luteal function as well as a paracrine role in angiogenesis.

Differentiation of malignant lymphoma and non-lymphoma by an occlusive dressing method employing bromodeoxyuridine.

Although lymphoma cells can proliferate in skin tissue, lymphocytes which have infiltrated the skin due to inflammatory changes are generally unable to do so. It may be possible to differentiate malignant lymphomas from benign lymphocytic infiltrations in skin tissue by detection of cell cycle-related antigens. We developed a novel in vivo method for studying the cell kinetics of human skin using bromodeoxyuridine (BrdU) with an occlusive dressing. Following the application of BrdU, BrdU-labeled lymphoid cells were counted in the dermis. The patients studied included 22 with various types of lymphomas (lymphoma group) and 22 with different forms of inflammatory skin disease (non-lymphoma group). Skin specimens were obtained after applying occlusive adhesive plasters containing 2% BrdU dissolved in 0.9% sodium chloride solution and were then immunostained with anti-BrdU monoclonal antibody. The average percentages of labeled cells were 15.9 +/- 7.6% for the lymphoma group and 4.7 +/- 2.6% for the non-lymphoma group. This difference was statistically significant (p < 0.0001). Using this method, malignant lymphomas and benign lymphocytic infiltrations of the skin could be differentiated by counting BrdU-labeled lymphoid cells, and this method could help in determining a prognosis.

Effect of transcatheter arterial chemoembolization on kidney hemodynamics and function in patients with cirrhosis and hepatocellular carcinoma.

BACKGROUND/AIMS: Transcatheter arterial chemoembolization (TACE) may have deleterious effect on the kidney in patients with cirrhosis and hepatocellular carcinoma. The aim of the study was to test this hypothesis. METHODS: Twenty-four patients with cirrhosis and hepatocellular carcinomas were included. They consisted of 16 patients undergoing a single TACE and eight patients undergoing diagnostic angiography. Doppler ultrasonography was used to measure hepatic artery pulsatility index (HA-PI) and renal artery pulsatility index (RA-PI) before and 1 day and 10 days after the procedure. Similarly, kidney function was assessed by measuring creatinine clearance. In addition, plasma renin activity, noradrenaline, and endothelin-1 were also measured. RESULTS: In patients receiving diagnostic angiography, no significant changes in HA-PI were observed after the procedure. In contrast, HA-PI increased significantly 1 day after the procedure (19%, p<0.01) in patients undergoing TACE, although it returned to baseline value 10 days after the procedure. In patients undergoing diagnostic angiography, no significant changes in RA-PI were observed after the procedure. Similarly, no detectable changes in RA-PI were noted in patients undergoing TACE. A transient small reduction in creatinine clearance was noted after the procedure in patients undergoing diagnostic angiography (-12%, p<0.05) and in those undergoing TACE (-11%, p<0.05). However, the effect was similar in the two groups (two-way ANOVA, p=0.72). No significant changes in plasma renin activity, noradrenaline, and endothelin-1 were observed after either diagnostic angiography or TACE. CONCLUSIONS: These results suggest that TACE per se has no deleterious effect on the kidney hemodynamics and function in patients with cirrhosis and hepatocellular carcinoma.

Transient increases of apoptosis and Bax expression occurring during radiotherapy in patients with invasive cervical carcinoma.

BACKGROUND: Apoptosis plays a crucial role in radiation therapy (RT) in various carcinomas. This study was designed to investigate the relation between apoptosis and RT in invasive squamous cell carcinoma (ISCC) of the uterine cervix METHODS: Thirty-five specimens were obtained from 7 patients with ISCC before and during a fractionated RT. The occurrence of apoptosis was examined by end labeling of DNA gel fractionation and in situ 3' end labeling of DNA. The expression of Bax and Bcl-2 proteins was investigated by immunohistochemical staining. RESULTS: Autoradiographic analysis revealed that high molecular weight DNA was predominant in the untreated ISCC specimens. However, a ladder-like pattern, characteristic of the apoptotic breakdown of DNA, was identified at doses of 900 cGy and 1980 cGy. At doses >1980 cGy, DNA laddering disappeared without any extensive smearing. Quantitative analysis of low molecular weight fragments of DNA revealed significant increases at doses of 900 cGy and 1980 cGy compared with those before RT and at doses of >1980 cGy. Labeling of DNA in situ indicated that cells undergoing apoptosis increased dramatically at a dose of 900 cGy. However, apoptotic cells decreased at a dose of 3960 cGy. In addition, a large fraction of tumor cells was immunonegative for Bcl-2 before and during RT. By contrast, immunoreactive Bax was observed intensely in many neoplastic cells at doses of 900 cGy and 1980 cGy. CONCLUSIONS: The current investigation indicates that low doses of RT result in apoptotic cell death in ISCC in association with the increased expression of Bax but not with increased Bcl-2 expression.

Mucosa-associated lymphoid tissue lymphoma of the duodenum forming multiple polypoid lesions: report of a case.

We report herein the case of a patient found to have mucosa-associated lymphoid tissue (MALT) lymphoma of the duodenum forming multiple polypoid lesions. Endoscopic examination revealed multiple small nodules with a yellow-white, rough surface in the duodenal bulb. Histopathological and immunological findings subsequently suggested low-grade B-cell MALT lymphoma. Cytologically, MALT lymphoma is similar to multiple lymphomatous polyposis (MLP); however, this case, which involved multiple polypoid lesions, was confirmed not to be MLP.

Cytotoxic T lymphocyte-mediated cell death in paraneoplastic sensory neuronopathy with anti-Hu antibody.

Paraneoplastic sensory neuronopathy (PSN) has been shown to harbor characteristic anti-neuronal autoantibody 'anti-Hu' in their sera and cerebrospinal fluid. Creation of animal models exhibiting clinical or pathological features seen in PSN by means of passive transfer of anti-Hu positive IgG has not been achieved. Although, anti-Hu antibody was shown to induce neuronal cell lysis in vitro, this result has not been reproduced so far. Since prominent T cell infiltration are seen in the central nervous system and posterior spinal ganglion of the patients with anti-Hu syndrome, we studied cytotoxic T cell (CTL) activity in peripheral mononuclear cells from a patient with PSN harboring anti-Hu antibody. The activated CD8+ T cells from the patient's venous blood were shown to lyse her own fibroblasts which were incubated with interferon-gamma to induce HLA class I molecules on their surface and the recombinant HuD protein was injected into the cells by microinjector. This is the first report showing the existence of CTL in a patient with PSN.

Apoptosis and the expression of Bax and Bcl-2 in squamous cell carcinoma and adenocarcinoma of the uterine cervix.

BACKGROUND: Apoptosis plays a crucial role in the suicide and turnover of cells in various tumors. This study was designed to investigate the relation between apoptosis and the histologic types of cell in invasive cervical carcinoma. METHODS: Cervical tissues were obtained from 19 patients with invasive squamous cell carcinoma (ISCC), 9 patients with invasive endocervical adenocarcinoma (IEAC), and 15 patients with myoma uteri (which were used as controls). Each tissue was rapidly frozen and/or fixed in Bouin's solution. The occurrence of apoptosis was examined by end labeling of DNA with (alpha-32P)dideoxyATP and electrophoretic fractionation and by end labeling of DNA in situ with digoxigenin-dideoxyUTP. The expression of Bcl-2 and Bax proteins was examined by immunohistochemical staining with appropriate antibodies. RESULTS: Autoradiographic analysis revealed that high molecular weight DNA was predominant in the normal cervical epithelium (NCE) and in ISCC. However, a ladder-like pattern of DNA fragments, characteristic of the apoptotic breakdown of DNA, was identified in IEAC. Quantitative analysis of low molecular weight fragments of DNA revealed a significant increase in IEAC but not in ISCC compared with NCE. Labeling of DNA in situ indicated that cells undergoing apoptosis were predominant among the neoplastic cells of IEAC. However, no apoptotic cells were noted in ISCC, with the exception of cells in some tumor nests. A large fraction of IEAC and ISCC was immunonegative for Bcl-2. Although the expression of Bax was detected weakly in a small fraction of ISCC, strong expression of Bax was observed in all cases of IEAC. CONCLUSIONS: Apoptosis appears to occur in the cancerous cells of invasive adenocarcinoma of the uterine cervix in association with a high level of expression of Bax but not of bcl-2.

Immunohistochemical localization of inhibin and activin subunits in human epithelial ovarian tumors.

OBJECTIVE: Our purpose was to examine the cellular localization of inhibin and activin subunits in human epithelial ovarian tumors. STUDY DESIGN: We examined the immunohistochemical localization of the alpha, betaA, and betaB subunits of inhibin in human mucinous and serous ovarian tumors including adenoma, cystic tumor with borderline malignancy, and adenocarcinoma. RESULTS: Immunostaining specific for the alpha, betaA, and betaB subunits of inhibin was observed in the tumor cells of the mucinous adenoma and the cystic tumor with borderline malignancy. We observed negative immunostaining specific for the alpha subunit and positive staining specific for the betaA and betaB subunits in the tumor cells of the mucinous adenocarcinoma. We did not observe any staining for the alpha subunit of inhibin in the serous tumors including benign adenoma, cystic tumor with borderline malignancy, and adenocarcinoma. However, positive staining results for the betaA and betaB subunits were observed in the serous tumor cells. CONCLUSION: Our results suggest that inhibins and activins might be secreted by the mucinous adenoma and the cystic tumor with borderline malignancy and that activins might be secreted by the mucinous adenocarcinoma and the serous tumors including benign adenoma, cystic tumor with borderline malignancy, and adenocarcinoma.