Carcinogenicity of 1,2-dimethylhydrazine dihydrochloride in BALB/c mice

Summary The carcinogenicity of 1,2-dimethylhydrazine dihydrochloride (DMH) by oral, intragastric and subcutaneous administration was examined in 339 BALB/c mice. Subcutaneous injection of DMH induced intestinal tumors in the lower colon of all mice. After oral administration it induced a high incidence of vascular tumors in the liver and soft tissues, but colon tumors were found in only 2 mice when given at a high dosage. On intragastric administration, it induced a fairly high incidence both of colon and vascular tumors. The sites and incidences of vascular tumors and squamous cell carcinomas of the perianal glands were also described.This work was supported in part by a Grant-in Aid for Cancer Research from the Ministry of Education, Japan.     

Giant inflammatory polyposis of the descending colon associated with a Crohn's disease-like colitis

A case of giant inflammatory polyposis associated with a localized inflammatory bowel disease of the descending colon in a 49-year-old man is presented. Lower abdominal distension rapidly appeared without any previous history of gastrointestinal disease. Two months later, he underwent a left hemicolectomy. Postoperative recovery was complete and he remains in good health more than 2 years later. The resected colon showed a giant and bizarre polyposis measuring up to 12 cm in length and 2 cm in height and covering the entire circumference of the colon. The polyposis consisted of narrow worm- or noodle-like polyps that bridged over the irregularly shaped ulcers, which sometimes extended into muscularis propria. Although longitudinal ulcers or scars, stricture, and a cobble-stone appearance were not observed, transmural inflammation and deep fissures were found in the interpolypoid area. From these findings, this case seems to be more similar to Crohn's disease than other inflammatory bowel diseases.     

The effectors of killer activity induced by interferon-alpha and gamma in peripheral blood mononuclear cells

The nature of effectors of interferon (IFN)-alpha or IFN-gamma-induced killer cell activity remains unclear. The aim of this study was to examine killer cell activity induced by IFN-alpha alone, IFN-gamma alone or a combination of both in patients with renal cell carcinoma (RCC) and to determine the phenotypic patterns of these effectors. The study group included 14 patients (12 men and 2 women, median age 64 years, range 36-77) with confirmed RCC. Peripheral blood mononuclear cells (PBMC) from RCC patients or normal volunteers were cultured with IFN-alpha alone, IFN-gamma alone or a combination of both. Cytotoxic activity was assayed against ACHN cells. Subpopulations of effector cells in IFN-induced killer cell activity were characterized by cell sorting. The most effective type of IFN and the optimal concentration of IFN necessary to induce the maximal killer cell activity varied among RCC patients. The killer activity induced by a combination of IFN-alpha and IFN-gamma was significantly greater than that induced by IFN-alpha or IFN-gamma alone. The greatly increased killer activity induced by IFN-alpha and IFN-gamma was seen in the subpopulations CD3(-) CD16(+), CD3(-) CD56(+) and subpopulation CD3(+)CD4(-), CD3(-)CD16(+), CD3(-)CD56(+), CD57(+)CD16(-), respectively. An optimal type of IFN and optimal concentration of IFN seem to increase the effective rate of treatment of RCC. In addition, the role of IFN-alpha seems to be different from that of IFN-gamma in host defense against RCC. A combination treatment with IFN-alpha and IFN-gamma seems to be suitable to increase the effective rate if we could reduce the side effects of IFNs.     

Age-dependent change in activities of lysosomal enzymes in rat brain

The age-dependent change in activities of seven lysosomal enzymes (cathepsin D, β-glucuronidase, acid phosphatase, acid/alkaline DNases and acid/alkaline RNases) was studied in four brain regions (cerebrum, hippocampus, pons and cerebellum) of Wistar rats. The activity of cathepsin D was significantly increased with aging in the four regions. The age-dependent change in activities of acid and alkaline DNases showed the characteristic regional difference, and the ratio of acid to alkaline DNases was increased with aging in all regions. Acid RNase showed the lowest activity in 18-month-old rats, and alkaline RNase activity was decreased with aging. The activity of β-glucuronidase was higher in 2-month-old rats in all of the regions studied. Acid phophatase showed no significant age-dependent change except in pons. The study demonstrated that all of the lysosomal enzyme activities do not change in parallel with aging, and that the age-dependent change showed the characteristic regional difference.     

Significance of aberrant (cytoplasmic/nuclear) expression of beta-catenin in pancreatoblastoma

This study concerns the significance of aberrant (nuclear/cytoplasmic) expression of beta-catenin in pancreatoblastoma (PBL). On immunohistochemistry, all seven PBLs examined showed nuclear/cytoplasmic expression of beta-catenin, predominantly in the squamoid corpuscles (SCs). In areas with acinar/ductular differentiation, few tumour cells displayed nuclear/cytoplasmic expression of beta-catenin and more than half of the tumour cells showed membranous expression. Two out of five (40%) tumours examined showed missense mutations in codons 33 and 37 of exon 3 of the beta-catenin gene. No mutation of the adenomatous polyposis coli (APC) gene was detected in two of the remaining three tumours. Amplifiable DNA for APC analysis was not obtained from the one other tumour. Immunoreactivity for cyclin D1, one of the nuclear targets of beta-catenin, was found predominantly in the SCs of the seven tumours. In contrast, the Ki-67 labelling index was 2-4% (median 3%) in the SCs and 8-18% (median 12%) in the other areas, indicating a negative correlation with nuclear cyclin D1 reactivity. These results imply that in PBLs, nuclear/cytoplasmic accumulation of beta-catenin and overexpression of its target gene cyclin D1 are not associated with the induction of tumour cell proliferation. Nuclear/cytoplasmic accumulation of beta-catenin may be related to the morphogenesis of the SCs that are considered most characteristic for PBL.     

Polymerization of 2-vinyl-1,3-dioxolane

When 2-vinyl-1,3-dioxolane was treated at low temperature (?78 or ?130°C.) with cationic catalysts, oily or semi-solid polymer was produced. The result of alkaline hydrolysis showed that the polymeric product contained ester units whose amount was about 2 to 15 mole-% of the total units. The remaining part of the polymer consisted of units containing the dioxolane ring. In the alkaline alcoholysis of the polymer with ethanol ethyl δ-hydroxyvalerate was formed. These findings indicate that in the low temperature cationic polymerization of 2-vinyl-1,3-dioxolane the ester unit, ? O(CH₂)₄CO? , is formed in addition to the unit of vinyl polymerization. A mechanism for the formation of the ester unit has been proposed, in which the process of hydride-shift is followed by ring-opening of the resulting carbonium ion species of dioxolane.     

Kupffer cell-mediated cytotoxicity against hepatoma cells occurs through production of nitric oxide and adhesion via ICAM-1/CD18

Rat Kupffer cell (KC)-mediated cytotoxicity against both thesyngeneic hepatoma cell line AH70 and hepatocytes was evaluatedby changes in mitochondrial function, and the possible roleof ICAM-1/CD18 in the interaction between the cells was studied.Rhodamine 123 fluorescence, a marker of the mitochondrial membranepotential, decreased in AH70 cells after co-culture with KC,while that in hepatocytes was unchanged by co-culture. Thisdecrease was blocked by anti-ICAM-1, anti-CD18 and the Inhibitionof nitric oxide synthesis. Cytometric studies demonstrated thatICAM-1 expression on AH70 cells increased after addition ofIFN-, IL-1ß, tumor necrosis factor (TNF)- or KC, whilein hepatocytes ICAM-1 was not increased. Anti-ICAM-1 pretreatmentinhibited the increase in ICAM-1 expression and the decreasein rhodamine 123 fluorescence on AH70 cells after co-culturewith KC. CD18 on KC was increased only after co-culture withAH70. TNF- but not IFN- was detected in the supernatant of co-culturebetween KC and AH70 cells, and this production was partiallyinhibited by anti-ICAM-1 and anti-CD18. The activity of Induciblenitric oxide synthase in Kupffer cells and the levels of nitritesand nitrates in the co-culture supernatant increased over time,and this increase was attenuated either by addition of NO synthesisinhibitors, anti-ICAM-1 or anti-CD18. These results indicatethat the rat KC causes mitochondrial dysfunction in cancer cellsvia the production of NO and cell-to-cell adhesion via ICAM-1/CD18has an Important role in this cytotoxic process.     

Membrane potential changes in vocal cord tensor motoneurons during breathing, vocalization, coughing and swallowing in decerebrate cats

We studied the patterns of membrane potential changes in vocal cord tensor motoneurons, i.e. cricothyroid muscle motoneurons (CTMs), during fictive breathing, vocalization, coughing, and swallowing in decerebrate paralyzed cats to determine the nature of central drives to CTMs during these behaviors. CTMs were identified by antidromic activation from the superior laryngeal nerve. During breathing, CTMs always depolarized during the inspiratory phase, and sometimes depolarized during the expiratory phase as well. During vocalization, CTMs strongly depolarized. During coughing, CTMs exhibited depolarizations during both inspiratory and expiratory phases, but it was interrupted by a transient repolarization between the last part of the inspiratory phase and the first part of the abdominal burst during which chloride-dependent inhibitory postsynaptic potentials were revealed. During swallowing, most CTMs hyperpolarized, and this hyperpolarization was sometimes followed by a weak depolarization. We conclude that the main role of the cricothyroid muscle is vocalization but the functional roles in coughing and swallowing are minor, and that the CTM activity during resting breathing and vocalization are primarily controlled by excitatory inputs, while during coughing and swallowing, inhibitory inputs play roles in shaping membrane potential trajectories.     

Seasonal malaria transmission and variation of anopheline density in two distinct endemic areas in Brazilian Amazonia

Studies on seasonal anopheline fauna variation were performed in two distinct settlements in the State of Rond?nia, Brazil: one at the Madeira River banks (Portuchuelo) with stable native Amazonian population; the other at an inland lumber-extracting farm (Urupá) in dry land, in which adults are mostly migrants. During a 6-yr period (1994-2000), 8,638 adult anophelines were collected: 2,684 in Urupá and 5,954 in Portuchuelo. Anopheles darlingi represented >95% of total mosquitoes caught. Dissection of 4,424 A. darlingi females yielded a very low sporozoite infection index below 0.1%. Oocysts were found in both localities in approximately 0.1% of dissected mosquitoes. Determination of the hour biting rates disclosed seasonal variations in both localities. However, in Portuchuelo, mosquito density peaked at the acme of the rainy season, whereas at Urupá it peaked in the dry season. The increase in mosquito density and incidence of malaria cases were coincident. The high mosquito densities observed in the riverine settlement of Portochuelo sector B, which permits evaluation in > 10,000 mosquitoes' bites/person/year, could explain, in spite of the low mosquito's infection index, the previously described development of natural immunity in the local population that is not observed in the dry land agroindustrial settlement of Urupá.