DNA ploidy pattern in diffuse infiltrating carcinomas of the stomach

Analysis of DNA ploidy patterns was performed on 76 diffusely infiltrating carcinomas of the stomach and the results correlated with histologic findings and outcome. Twenty six cases were diploid (34%) and 50 cases were aneuploid. There was no correlation between DNA ploidy and histologic type, depth of invasion, lymphatic invasion, evidence of peritoneal dissemination or curability. In aneuploid tumors, incidence of vascular invasion was significantly higher than that in diploid tumors (p less than 0.05). In addition, the patients with aneuploid tumors had a poor prognosis than with diploid tumors. These results indicate that DNA ploidy patterns may possibly be a useful prognostic marker for diffusely infiltrating carcinomas of the stomach.     

Histochemical study of pituitary adenomas with Ki-67 and anti-DNA polymerase α monoclonal antibodies,bromodeoxyuridine labeling,and nucleolar organizer region counts

Summary The growth potential of 65 pituitary adenomas was determined by histochemical analysis with Ki-67 and anti-DNA polymerase monoclonal antibodies, bromodeoxyuridine (BrdUdR) labeling, and counts of argyrophilic nucleolar organizer regions (Ag-NORs). The mean proliferating cell indices (PCIs) determined by Ki-67 and anti-DNA polymerase and the BrdUdR labeling index (LI) were generally very low [1.0±0.2%, 1.1±0.2%, and 0.5±0.1% (±SE), respectively]. Apart from adrenocorticotropic hormone-positive adenomas, which had significantly higher indices, there were no statistically significant differences in the indices among the other subtypes of pituitary adenomas. Recurrent tumors had higher Ki-67 and DNA polymerase PCIs and BrdUdR LIs (3.6%, 4.2%, 1.4%) than primary tumors (0.8%, 0.8%, 0.3%; P<0.005). The number of Ag-NORs did not correlated significantly with any of the three indices. The mean number of Ag-NORs was higher in nonfunctioning adenomas than in functioning adenomas (2.04 vs 1.66, P<0.005); among prolactin-positive adenomas, those treated preoperatively with bromocriptine had more Ag-NORs than untreated tumors (1.75 vs 1.57, P<0.005). These results suggest that the Ki-67 and DNA polymerase PCIs and the BrdUdR LI predict the growth potential of individual pituitary adenomas, whereas the number of Ag-NORs appears to correlate with hormone production rather than with the proliferative potential.Supported by grants CA-13525 and CA-50210 from the National Cancer Institute, by a grant from the Phi Beta Psi Sorority, and by Grant-in-Aid A 63771083 from the Ministry of Education, Science, and Culture of Japan     

Elective cesarean as a risk factor for transfusion after delivery of twins

We examined deliveries of twins to identify factors most strongly associated with an increased risk of transfusion. We reviewed the obstetric records of 511 twin deliveries at the Japanese Red Cross Katsushika Maternity Hospital from 2003 through 2007. After 18 (3.5%) of these deliveries, transfusions were required. Transfusion was significantly more likely after elective cesarean delivery at a gestational aged of 37 weeks or more (odds ratio, 4.85; 95% confidence interval, 1.87-12.61). Emergency cesarean delivery (at > or =37 weeks' gestation) was not associated with an increased risk of transfusion. The delivery mode of twins should be carefully considered because of the increased risk of transfusion after elective cesarean delivery at a gestational age of 37 weeks or more.     

Clostridium sordellii phospholipase C: gene cloning and comparison of enzymatic and biological activities with those of Clostridium perfringens and Clostridium bifermentans phospholipase C

The gene encoding Clostridium sordellii phospholipase C (Csp) was cloned and expressed as a histidine-tagged (His-tag) protein, and the protein was purified to compare its enzymatic and biological activities with those of Clostridium perfringens phospholipase C (Cpa) and Clostridium bifermentans phospholipase C (Cbp). Csp was found to consist of 371 amino acid residues in the mature form and to be more homologous to Cbp than to Cpa. The egg yolk phospholipid hydrolysis activity of the His-tag Csp was about one-third of that of His-tag Cpa, but the hemolytic activity was less than 1% of that of His-tag Cpa. His-tag Csp was nontoxic to mice. Immunization of mice with His-tag Cbp or His-tag Csp did not provide effective protection against the lethal activity of His-tag Cpa. These results indicate that Csp possesses similar molecular properties to Cbp and suggest that comparative analysis of toxic and nontoxic clostridial phospholipases is helpful for characterization of the toxic properties of clostridial phospholipases.     

Enhanced invasion of Tax-expressing fibroblasts into the basement membrane is repressed by phosphorylated ascorbate with simultaneous decreases in intracellular oxidative stress and NF-kappa B activation

Invasion of rat fibroblastic cells Rat-1 through Matrigel was shown to be promoted by transfection with tax gene of human T-cell leukemia virus type 1. We found that an oxidation-resistant type of vitamin C (Asc), Asc-2-O-phosphate (Asc2P), inhibited the invasion of the tax-transfected Rat-1 cells (W4 cells). Intracellular Asc (Ascin), after enzymatic dephosphorylation of administered Asc2P, was more abundant in W4 cells than in Rat-1 cells, and the ratio of dehydroascorbic acid versus Asc was increased in W4 cells but scarcely in Rat-1 cells, according to the enhanced level of intracellular reactive oxygen species (ROSin) in W4 cells. Asc2P notably repressed the increases in both ROSin and secretion of matrix metalloproteases (MMPs), but did not affect Tax protein expression in tax-transfectants. NF-kappa B activation, as evidenced by its translocation to the nucleus in W4 cells, was also repressed by Asc2P. Thus, the tax-promoted invasion together with the enhanced production of MMPs occurred with NF-kappa B activation and the increase in ROSin, both of which were effectively reduced by Asc2P. These findings indicate the therapeutic efficacy of Ascin-enriching agents for the prevention against tumor invasion in which ROSin plays a major role.     

Functional monomers and polymers, 105. Synthesis of poly(β-alanine) from a new type of active amino acid ester

Active β-alanine esters having dipeptide groups, which are capable of forming hydrogen bonds between the side chains, were prepared in the form of hydrogen chloride salts. The polycondensation of these salts was studied in non-polar solvents, in the presence of triethylamine. In the case of the ester with β-alanyl-β-alanine as dipeptide moiety, the polycondensation proceeded smoothly in chloroform solution. To explain the characteristic feature of the polycondensation, an ordered aggregation of the ester molecules is assumed to play an important role. The ester with glycylglycine as dipeptide moiety, however, did not undergo a polycondensation.     

Elevated nasal mucosal G protein levels and histamine receptor affinity in a guinea pig model of nasal hyperresponsiveness

BACKGROUND: Nasal hyperresponsiveness is a common feature of allergic rhinitis, but the underlying mechanisms have yet to be elucidated. The effects of repeated antigen inhalation on the characteristics of histamine H(1) receptors and expression levels of heterotrimeric guanosine 5'-triphosphate-binding proteins in nasal mucosa were investigated to understand the mechanisms of the pathogenesis of nasal hyperresponsiveness in allergic rhinitis. METHODS: Male Hartley guinea pigs were sensitized by the inhalation of dinitrophenylated ovalbumin antigen (10 mg of protein/ml) and repeatedly challenged by inhaling aerosolized dinitrophenylated ovalbumin antigen for 3 weeks. Twenty-four hours after the last antigen inhalation, in vivo nasal responsiveness to histamine was measured. [(3)H]Mepyramine binding assays and immunoblotting for alpha subunits of the G(q) protein were also performed using membrane preparations of isolated nasal mucosae. RESULTS: The histamine-induced increase in intranasal pressure was significantly augmented after repeated antigen challenge, indicating that nasal hyperresponsiveness was achieved. In saturation binding studies, no significant change was observed in the density and antagonist affinity of H(1) receptors in the hyperresponsive animals. On the other hand, the affinity of histamine for high-affinity agonist binding sites in the hyperresponsive group, measured by histamine competition binding studies, was much greater than that in control animals, and these results were affected by guanosine 5'-O-(3-thiotriphosphate) in both groups. Moreover, Galpha(q) levels in nasal mucosal homogenates were significantly increased after repeated antigen challenge. CONCLUSIONS: Elevated G protein levels in nasal mucosa might induce an increased binding affinity of histamine to its receptors, resulting in an augmented nasal response to histamine, that is, nasal hyperresponsiveness, in guinea pigs.     

Three Kinds of Foamy Cells in the Spleen: Comparative Histochemical and Ultrastructural Studies

By light and electron microscopy, we observed foamy cells in the spleens from a patient with hemolytic anemia due to red cell adenosine deaminase (ADA) overproduction, a patient with rheumatoid arthritis (RA) treated with gold, and patients with idiopathic thrombocytopenic purpura (ITP)

The foamy cells associated with red cell ADA overproduction were essentially similar to Gaucher-like cells described in patients with thalassemia, and it was suggested that the accelerated destruction of red cells was one of the factors responsible for the development of foamy cells. Foamy cells in ITP and RA were closely associated with an increased destruction of platelets in the spleen. Morphologic transitions between phagocytosed platelets and myelinlike materials were traced in these disorders. In RA, however, foamy cells were heterogeneous from an ultrastructural standpoint, with different cytoplasmic inclusions. In addition to myelinlike materials, dense bodies, vacuoles with flocculent materials, and gold were noted in most of foamy cells. As gold compounds are known to inhibit lysosomal enzymes, we surmise that an acquired disturbance in lysosomal digestion is partially responsible for the accumulation of intermediate metabolites.

In the pathogenesis of foamy cells associated with blood cell dyscrasia, the accelerated destruction of blood cells and/or acquired disorders in catabolic pathways within the macrophages are suggested to be the underlying mechanism of an intralysosomal accumulation of incompletely degraded cellular debris.