The Japanese journal of experimental medicine最新文献

The expression of the erbB-2 gene product was studied immunohistochemically on 38 normal colonic mucosae, 14 adenomas and 44 colon cancers, with the use of two anti-erbB-2 antibodies, a rabbit polyclonal antibody specific for the intracellular domain and a mouse monoclonal antibody specific for the extracellular domain. Normal mucosae and adenomas were not stained. Five cases (11%) of colon cancer were positive with the polyclonal anti-erbB-2 antibody, while only one case was positive with the monoclonal antibody. Most of the positive cases were in Dukes C stage. The rare overexpression of the erbB-2 protein in colon cancer seems to indicate a minor role for the gene in colorectal tumorigenesis.

The characterization and change of lipids in aorta with the progression of atherosclerosis were elucidated in Watanabe hereditable hyperlipidemic (WHHL) rabbit, an animal model for human familial hypercholesterolemia as compared with those of normal rabbits. The amount of total phospholipids in the aorta of WHHL rabbit increased about 6-fold that of normal level. Sphingomyelin showed the largest increase and phosphatidylcholine the second in the aorta of WHHL rabbit. The fatty acid composition of sphingomyelin was characteristic of higher content of unsaturated fatty acids. It was suggested that the specific increase in both sphingomyelin and its unsaturated fatty acid content might be ascribed to regulation mechanism to recover the membrane fluidity which was reduced by the marked accumulation of cholesterol in the aorta of WHHL rabbit. Glycerophospholipids in the aorta of WHHL rabbit also contained more unsaturated fatty acids than those in normal ones. It was suggested that the higher amounts of unsaturated fatty acids of glycerophospholipids might be derived from those of serum lipoproteins and that they also might help to restore or recover membrane fluidity in the cholesterol-accumulated aorta of WHHL rabbit. Phosphatidylcholine in the aorta of WHHL rabbit contained a large amount of alkylacyl type-homologue (25-fold normal level) which was a precursor of platelet-activating factor (PAF). The increase of lysophosphatidylcholine, a potent chemotactic factor for monocyte, was also observed in WHHL rabbit. The increase of these chemical mediators indicated severe pathologic state in the atherosclerotic lesions of the aorta of WHHL rabbit.

In the preceding papers, we showed that the treatment of BALB/c mice with 12-O-tetradecanoylphorbol 13-acetate (TPA), a typical tumor promoter, suppressed footpad reaction (FPR) against sheep red blood cells (SRBC) temporarily but that this effect became lasting when TPA was administered to mice which had been treated with 7,12-dimethyl[a]-anthracene (DMBA), a typical tumor initiator, and that the effect of DMBA and TPA was caused by the induction of antigen-nonspecific T suppressor cells. In this work, we studied the effect of anthralin, a tumor promoter which has not the structure of phorbol ester, on FPR of BALB/c mice against SRBC. Painting of anthralin (80 nmol) suppressed FPR continuously (more than 7 days) unlike that of TPA. However, when anthralin was administered for 7 days following the treatment with 400 nmol of DMBA, the suppressive effect could be transferred with Thy-1 and Lyt-2 positive spleen cells whereas the suppressive effect by the painting of anthralin only for 7 days could not be transferred with the spleen cells.

In the epidemiological surveys on scrub typhus at Chichibu City near Tokyo, an area, 350 m by 35 m, in the Hitsujiyama Park was found to be heavily infested with Rickettsia tsutsugamushi (Rt). Distribution of trombiculid mites and their infection rates in this area were studied using sentinel animals, 48 Microtus montebelli and 10 ddY mice. The surveys were conducted 6 times in the autumn in 1985 and 1986. At the first 2 surveys, 16 animals were placed at random, and 4 restricted areas were identified as highly populated with trombiculid mites. For the detailed survey, each of 4 areas was divided into 2 m x 2 m quadrats to settle a sentinel animal to each. A total of mites collected by all sentinel animals was 331 Leptotrombidium pallidum, 175 L. fuji and 16 Gahrliepia saduski. Almost all mites were collected by M. montebelli, except only 1 L. fuji in 10 mice. From a M. montebelli in a quadrat, 157 L. pallidum were recovered, whereas the number/vole was 0 to 24 in the others. L. fuji was also highly aggregated at 2 sites. Rt was detected from individual mites by avidin-biotin immunofluorescence or isolated by the mouse passage from individual or pooled mites. Only Karp strain of Rt was detected or isolated from L. pallidum at a ratio of 31/286 (10.8%). No Rt was found from L. fuji or G. saduski. The infection rate in L. pallidum was especially high in 3 voles at ratios of 6/11, 2/5 and 3/5, respectively. Out of 14 sentinel M. montebelli with infected L. pallidum, 12 (85.7%) were infected with Rt. It was concluded that L. pallidum was distributed in aggregated clusters to form the mite islands and was infected heavily at the specific sites to make the infective spots.

The influence of the oxidizing agents (H2O2, KO2 and Vitamin K) on the action of vasopressin to guinea pig hepatocytes was investigated from the view-point of cytoplasmic Ca2+ concentration and protein secretion. 10 nmol/l vasopressin brought about increase in prothrombin secretion along with increase in the cytoplasmic Ca2+ concentration compared to the non-stimulation level. The pretreatment of the cells with 1 mumol/l of the oxidizing agents, however, led to suppression of Ca2+ elevation and inhibited the vasopressin-induced prothrombin secretion completely, while no leak if lactic dehydrogenase (LDH), Na+ and K+ were detected. The same results of the inhibition in fibrinogen and albumin secretion were observed. These results suggested a possibility that the oxidizing agents such as the peroxides act on some site of cellular signal transduction system in cell membrane to reduce the cytoplasmic Ca2+ level and to suppress the vasopressin-induced secretion.

An approach has been made to develop an in vitro screening system to evaluate antifilarial efficacy of compounds and an effort has been made to establish correlation between in vivo and in vitro screening technique. The in vitro experiments were conducted simultaneously using three life-forms (adult, microfilaria and infective larva) of Acanthocheilonema viteae using five antifilarial agents representing four chemical groups. All the selected antifilarials were known to be active against one or more life-stages of human lymphatic or animal filariids. Diethylcarbamazine and Centperazine showed 100% microfilaricidal and infective larvicidal actions at concentrations of 0.5 and 0.25 mg/ml and 0.5 and 0.0313 mg/ml respectively with no effect on adult worms even at 1 mg/ml. Levamisole was effective against all the three life-stages killing 100% adult worms at 1 mg/ml, infective larvae at 0.0625 mg/ml and microfilariae at 0.0125 mg/ml, while mebendazole exhibited activity only against adult worms (100% at 0.5 mg/ml). Ivermectin killed adult females and microfilariae at 0.063 and 0.5 mg/ml respectively but did not affect infective larvae even up to 1 mg/ml concentration. The study indicated that in vitro screening system can be used for primary screening of potential antifilarial agents provided three life-forms of A. viteae are used simultaneously to avoid false negative results. It would however be more appropriate if a few compounds of a particular chemical class are initially assessed both in vivo and in vitro for validity of subsequent test results in vitro.

Long term effects of adult-thymectomy on both natural killer (NK) activity and spontaneous tumor incidence were investigated in C57BL/6 mice maintained in specific pathogen free atmosphere. As compared with the age matched sham-thymectomized mice, a substantially low incidence of spontaneous tumour (6%) and a high level of splenic NK activity were noted one and a half year later in C57BL/6 mice thymectomized at 6 weeks of age. In contrast, sham-thymectomized mice showed a high incidence of the spontaneous tumor (57%) associated with a low level of splenic NK activity. These results suggest that NK cells play a critical role to prevent the occurrence of spontaneous tumor in vivo.

Two mono-sulfated glycosphingolipids were isolated from the human amnion. By carbohydrate analysis and acid hydrolysis, the structure of these glycolipids are proposed to be galactosylsulfatide (SM4s) and lactosylsulfatide (SM3). The major fatty acids of SM4s and SM3 were C16:0. The yields of SM4s and SM3 from the amnion were about 340 and 110 pmol/g wet wt, respectively.